Browsing by Author "Miljković, Branislava (6602266729)"

Objective: Cardiovascular disease (CVD) drugs have been frequently implicated in adverse drug reaction (ADR)-related hospitalizations. Drug–drug interactions (DDIs) are common preventable cause of ADRs, but the impact of DDIs in the CVD population has not been investigated. Hence, the primary aim of the study was to identify DDIs associated with ADRs in CVD patients at hospital admission. The second aim was to develop a simple tool to identify high-risk patients for DDI-related adverse events. Methods: An observational study was conducted on the Cardiology Ward of University Clinical Hospital Center. Data were obtained from medical charts. A clinical panel identified DDIs implicated in ADRs, using LexiInteract database and Drug Interaction Probability Scale. Statistics were performed using PASW 22 (SPSS Inc.). Results: DDIs contributed to hospital admission with a total prevalence of 9.69%. DDI-related ADRs affected mainly cardiac function (heart rate or rhythm, 41.07%); bleeding and effect on blood pressure were equally distributed (17.86%). Non-cardiovascular ADRs were found in 23.21% of DDIs. After admission, 73% of the identified DDIs led to changes in prescription. Prediction ability of calculated DDI adverse event probability scores was rated as good (AUC = 0.80, p <.001). Conclusions: CVD patients are highly exposed to adverse DDIs; about one in ten patients hospitalized with CVD might have a DDI contributing to the hospitalization. Given the high prevalence of CVD, DDI-related harm might be a significant burden worldwide. Identification of patients with high DDI adverse event risk might ease the recognition of DDI-related harm and improve the use of electronic databases in clinical practice. © 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group.

Objectives: To identify changes in prescribing patterns of antibiotic prophylaxis in Caesarean delivery after introduction of local clinical guidelines. To identify changes in outcomes of prescribing antibiotics following the implementation of local clinical guidelines on antibiotic prophylaxis. Setting: University of Belgrade, Medical School, Clinic of Gynaecology and Obstetrics "Narodni front" Belgrade, Serbia. Method: A quantitative retrospective analysis of antibiotic use before (January-June 2005), and following (January-June 2006) implementation of guidelines on antibiotic prophylaxis in two wards. Patients who underwent Caesarean section prior to (261) and following (281) introduction of local guidelines, participated in this study. Main outcome measures: Drug utilization cost presented as the number of DDD/100 bed days/eur, the average duration of hospital stay, number of wound infections. Results: There was a significant change in prescribing patterns of antibiotic prophylaxis in Caesarean section following introduction of local guidelines. The use of ceftriaxone, amikacin and metronidazole decreased (57.47% vs. 11.74%; 9.19% vs. 4.27%; 61.69% vs. 46.26%, respectively). On the other hand, the use of "older" antibiotics such as gentamicin, cefuroxime, cefazolin and ampicillin increased (14.56% vs. 29.18%; 9.2% vs. 17.44%; 9.58% vs. 45.2% and 0% vs. 3.9%, respectively). DDD/100 bed days/eur analysis revealed a 47% decrease of total cost for prophylactic antibiotic treatment in Caesarean section following local guideline implementation. In contrast, rate of wound infections and duration of hospital stay were not significantly different in both groups. Conclusion: In an attempt to ensure cost-effective prophylactic use of antibiotics in Caesarean delivery, local clinical guidelines were introduced. They resulted in changes in prescribing patterns of antibiotics. There was a significant decrease in use of 'third' generation of cephalosporin's whereas the use of "older" antibiotics with proven efficacy and safety increased. In contrast, there was no significant change in treatment outcomes such as wound infection and average hospital stay. © Springer Science+Business Media B.V. 2009.

Objectives: To identify changes in prescribing patterns of antibiotic prophylaxis in Caesarean delivery after introduction of local clinical guidelines. To identify changes in outcomes of prescribing antibiotics following the implementation of local clinical guidelines on antibiotic prophylaxis. Setting: University of Belgrade, Medical School, Clinic of Gynaecology and Obstetrics "Narodni front" Belgrade, Serbia. Method: A quantitative retrospective analysis of antibiotic use before (January-June 2005), and following (January-June 2006) implementation of guidelines on antibiotic prophylaxis in two wards. Patients who underwent Caesarean section prior to (261) and following (281) introduction of local guidelines, participated in this study. Main outcome measures: Drug utilization cost presented as the number of DDD/100 bed days/eur, the average duration of hospital stay, number of wound infections. Results: There was a significant change in prescribing patterns of antibiotic prophylaxis in Caesarean section following introduction of local guidelines. The use of ceftriaxone, amikacin and metronidazole decreased (57.47% vs. 11.74%; 9.19% vs. 4.27%; 61.69% vs. 46.26%, respectively). On the other hand, the use of "older" antibiotics such as gentamicin, cefuroxime, cefazolin and ampicillin increased (14.56% vs. 29.18%; 9.2% vs. 17.44%; 9.58% vs. 45.2% and 0% vs. 3.9%, respectively). DDD/100 bed days/eur analysis revealed a 47% decrease of total cost for prophylactic antibiotic treatment in Caesarean section following local guideline implementation. In contrast, rate of wound infections and duration of hospital stay were not significantly different in both groups. Conclusion: In an attempt to ensure cost-effective prophylactic use of antibiotics in Caesarean delivery, local clinical guidelines were introduced. They resulted in changes in prescribing patterns of antibiotics. There was a significant decrease in use of 'third' generation of cephalosporin's whereas the use of "older" antibiotics with proven efficacy and safety increased. In contrast, there was no significant change in treatment outcomes such as wound infection and average hospital stay. © Springer Science+Business Media B.V. 2009.

Background and Aim: Adverse effects are common in children treated with antiepileptic medications and may affect parental beliefs about treatment. The aim of the study was to investigate the relationship between adverse effects and parental beliefs about antiepileptic drugs used for the treatment of their children. Methods: The study was performed at the University Children’s Hospital, Belgrade, Serbia from 2013–2015. Parents of children treated with valproic acid, carbamazepine or lamotrigine, were eligible. They were asked to fill in the Beliefs about Medications Questionnaire (BMQ) and The Liverpool Adverse Events Profile (LAEP). Results: Parents of 127 children (average age 9.88 ± 4.16 years) of whom 111 had epilepsy (67 generalized, 44 focal) and 16 with febrile seizures participated in the study. Nervousness and/or agitation, weight gain, restlessness, headache, difficulty in concentrating, feeling of aggression and upset stomach were most frequent adverse effects, reported in 37% of the population. BMQ-specific necessity scores significantly correlated with parental education; parents with elementary school showed lower scores than those with higher education. The presence of difficulty in concentrating of their child was associated with higher BMQ concern scores (20.73 ± 4.25 vs. 18.99 ± 3.60, p = 0.043) as well as necessity scores (18.42 ± 3.31 vs. 16.40 ± 2.73, p = 0.017). Higher scores of BMQ-general overuse were reported in the presence of a headache (8.79 ± 2.81 vs. 7.64 ± 2.72, p = 0.027). Conclusions: The main finding of our study is that parental beliefs about antiepileptic drugs were associated with the presence of adverse effects. Understanding this relationship could allow physicians and pharmacists to structure better educational programs for parents of children treated with antiepileptic drugs. Education should be more focused towards understanding the adverse effects of antiepileptics which could alleviate parental concerns and strengthen their beliefs about the necessity of medication use in their children. © 2018 by the authors. Licensee MDPI, Basel, Switzerland.

Purpose: The goal of the study was to examine clozapine (CLZ) and norclozapine (NCLZ) therapeutic drug monitoring (TDM) data and associated sources of pharmacokinetic variability, particularly the impact of valproic acid (VPA) use. Methods: This study included 126 patients with psychiatric disorders on mono- or co-therapy with CLZ. Patients’ data during routine TDM were collected retrospectively from clinical records. The descriptive and statistical analysis was computed using IBM SPSS Statistics software (version 22, NY, USA). Multiple linear regression, based on the last observations, was used to assess correlation between demographic characteristics, life habits and co-therapy with dose-corrected serum levels (C/D) of CLZ and NCLZ, as well as CLZ/NCLZ. Results: A total of 295 CLZ concentrations were measured in 126 patients, with a mean of 275.5 ± 174.4 µg/L, while 124 NCLZ concentrations were determined in 74 patients, with a mean of 194.6 ± 149.8 µg/L. A statistically significant effect on ln-transformed CLZ C/D was confirmed for sex and smoking, whereas sex, smoking and VPA therapy were associated with ln-transformed NCLZ C/D. According to the final models, lower values of NCLZ C/D for about 45.9% can be expected in patients receiving VPA. Concomitant use of VPA was the only factor detected to contribute in CLZ/NCLZ variability. Conclusion: The results of this study may help clinicians interpret TDM data and optimize CLZ dosing regimens, especially in patients concomitantly treated with VPA. Our results show that VPA primarily decreases NCLZ levels, while alteration of the parent drug is not statistically significant. © 2023, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Purpose: The goal of the study was to examine clozapine (CLZ) and norclozapine (NCLZ) therapeutic drug monitoring (TDM) data and associated sources of pharmacokinetic variability, particularly the impact of valproic acid (VPA) use. Methods: This study included 126 patients with psychiatric disorders on mono- or co-therapy with CLZ. Patients’ data during routine TDM were collected retrospectively from clinical records. The descriptive and statistical analysis was computed using IBM SPSS Statistics software (version 22, NY, USA). Multiple linear regression, based on the last observations, was used to assess correlation between demographic characteristics, life habits and co-therapy with dose-corrected serum levels (C/D) of CLZ and NCLZ, as well as CLZ/NCLZ. Results: A total of 295 CLZ concentrations were measured in 126 patients, with a mean of 275.5 ± 174.4 µg/L, while 124 NCLZ concentrations were determined in 74 patients, with a mean of 194.6 ± 149.8 µg/L. A statistically significant effect on ln-transformed CLZ C/D was confirmed for sex and smoking, whereas sex, smoking and VPA therapy were associated with ln-transformed NCLZ C/D. According to the final models, lower values of NCLZ C/D for about 45.9% can be expected in patients receiving VPA. Concomitant use of VPA was the only factor detected to contribute in CLZ/NCLZ variability. Conclusion: The results of this study may help clinicians interpret TDM data and optimize CLZ dosing regimens, especially in patients concomitantly treated with VPA. Our results show that VPA primarily decreases NCLZ levels, while alteration of the parent drug is not statistically significant. © 2023, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

The choice of an antiepileptic drug (AED) is usually based upon the epileptic seizure type. However, pharmacokinetic (PK) characteristics of AEDs may be valuable support in choosing the optimal therapeutic option for the individual patient. The novel (second and third generation) AEDs include: eslicarbazepine acetate, felbamate, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, rufinamide, stiripentol, tiagabine, topiramate, vigabatrin, and zonisamide. Although, these drugs belong to the same group, their individual PK characteristics differ. Gabapentin, unlike other new AEDs, is characterised by dose-dependent absorption, which is presumably caused by saturable L-amino acid transport system, and therefore its bioavailability ranges from 35-60%. Furthermore, gabapentin, pregabalin and vigabatrin are eliminated completely, while levetiracetam and topiramate are eliminated predominantly through the renal system. Therefore, PK variability of these individual drugs is less pronounced and more predictable in comparison to older AEDs. Their potential for drug interactions is minor, and consequently they have major clinical importance for patients with impaired hepatic function. On the other hand, felbamate, lamotrigine, oxcarbazepine, tiagabine and zonisamide are eliminated via metabolic pathways, either cytochrome P (CYP) 450, or conjugation dependent transformation. Oxcarbazepine is a prodrug, and its active metabolite is licarbazepine. These drugs interact with other drugs, and disease conditions, which alter the activity of metabolic enzymes; thus these changes in PK commonly have clinical implications. Gabapentin, levetiracetam and tiagabine do not induce or inhibit hepatic metabolism enzymes. Felbamate demonstrated an inducing effect on CYP 3A4 isoenzyme, and inhibition effect on CYP 2C19 and on β-oxidation of valproic acid. Lamotrigine induces its own metabolism, and some reports imply a decrease of valproic acid levels during concomitant treatment with lamotrigine. Oxcarbazepine induces CYP 3A4, 3A5, and uridine diphosphate glucuronyl transfereases (UGT), and inhibits the metabolism of phenytoin via CYP 2C19 isoenzyme. Similar induction and inhibition characteristics are attributed to topiramate, while some studies indicate that zonisamide may have inhibition potential on phenytoin metabolism. In general, novel AEDs have linear PK, low plasma protein binding, and renal elimination, so their PK is more favorable in comparison with carbamazepine, phenobarbitone and valproic acid. This chapter gives a review of PK parameters of novel AEDs and its' variability based on age, comorbidities, concomitant therapy, and highlights the need of therapeutic drug monitoring. © 2012 Nova Science Publishers, Inc. All rights reserved.

The choice of an antiepileptic drug (AED) is usually based upon the epileptic seizure type. However, pharmacokinetic (PK) characteristics of AEDs may be valuable support in choosing the optimal therapeutic option for the individual patient. The novel (second and third generation) AEDs include: eslicarbazepine acetate, felbamate, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, rufinamide, stiripentol, tiagabine, topiramate, vigabatrin, and zonisamide. Although, these drugs belong to the same group, their individual PK characteristics differ. Gabapentin, unlike other new AEDs, is characterised by dose-dependent absorption, which is presumably caused by saturable L-amino acid transport system, and therefore its bioavailability ranges from 35-60%. Furthermore, gabapentin, pregabalin and vigabatrin are eliminated completely, while levetiracetam and topiramate are eliminated predominantly through the renal system. Therefore, PK variability of these individual drugs is less pronounced and more predictable in comparison to older AEDs. Their potential for drug interactions is minor, and consequently they have major clinical importance for patients with impaired hepatic function. On the other hand, felbamate, lamotrigine, oxcarbazepine, tiagabine and zonisamide are eliminated via metabolic pathways, either cytochrome P (CYP) 450, or conjugation dependent transformation. Oxcarbazepine is a prodrug, and its active metabolite is licarbazepine. These drugs interact with other drugs, and disease conditions, which alter the activity of metabolic enzymes; thus these changes in PK commonly have clinical implications. Gabapentin, levetiracetam and tiagabine do not induce or inhibit hepatic metabolism enzymes. Felbamate demonstrated an inducing effect on CYP 3A4 isoenzyme, and inhibition effect on CYP 2C19 and on β-oxidation of valproic acid. Lamotrigine induces its own metabolism, and some reports imply a decrease of valproic acid levels during concomitant treatment with lamotrigine. Oxcarbazepine induces CYP 3A4, 3A5, and uridine diphosphate glucuronyl transfereases (UGT), and inhibits the metabolism of phenytoin via CYP 2C19 isoenzyme. Similar induction and inhibition characteristics are attributed to topiramate, while some studies indicate that zonisamide may have inhibition potential on phenytoin metabolism. In general, novel AEDs have linear PK, low plasma protein binding, and renal elimination, so their PK is more favorable in comparison with carbamazepine, phenobarbitone and valproic acid. This chapter gives a review of PK parameters of novel AEDs and its' variability based on age, comorbidities, concomitant therapy, and highlights the need of therapeutic drug monitoring. © 2012 Nova Science Publishers, Inc. All rights reserved.

Aim. To identify potential risk factors for the development of subclinical hypothyroidism following long-term valproic acid monotherapy in children with epilepsy. Methods. Serumlevels of thyroid-stimulating hormone, free thyroxine, free triiodothyronine, thyreoglobulin antibodies, and thyroid peroxidase antibodies were determined in 41 patients and in 41 sex- And age-matched healthy children. Results. Meanvalproic acid treatment durationwas 2.80?}1.96 years. The valproic acid group had higher serum thyroid-stimulating hormone (p<0.001) and free triiodothyronine (p<0.05) levels compared to the control group. Serum thyroid-stimulating hormone and free triiodothyronine were above the upper limit for healthy controls in 34% and 32% of patients, respectively, and no clinical features of thyroid dysfunction were observed. Duration of valproic acid monotherapy for less than four years was a risk factor for elevated thyroid-stimulating hormone levels. Conclusion. One third of children with normal range serum valproic acid levels may have elevated serum thyroid-stimulating hormone and free triiodothyronine levels, especially in the first four years of treatment.

Aim. To identify potential risk factors for the development of subclinical hypothyroidism following long-term valproic acid monotherapy in children with epilepsy. Methods. Serumlevels of thyroid-stimulating hormone, free thyroxine, free triiodothyronine, thyreoglobulin antibodies, and thyroid peroxidase antibodies were determined in 41 patients and in 41 sex- And age-matched healthy children. Results. Meanvalproic acid treatment durationwas 2.80?}1.96 years. The valproic acid group had higher serum thyroid-stimulating hormone (p<0.001) and free triiodothyronine (p<0.05) levels compared to the control group. Serum thyroid-stimulating hormone and free triiodothyronine were above the upper limit for healthy controls in 34% and 32% of patients, respectively, and no clinical features of thyroid dysfunction were observed. Duration of valproic acid monotherapy for less than four years was a risk factor for elevated thyroid-stimulating hormone levels. Conclusion. One third of children with normal range serum valproic acid levels may have elevated serum thyroid-stimulating hormone and free triiodothyronine levels, especially in the first four years of treatment.

Due to wide intra-and inter-individual pharmacokinetic variability and narrow therapeutic index of sirolimus, the therapeutic drug monitoring (TDM) of sirolimus with detailed biochemical and clinical monitoring is necessary for dose individualization in kidney transplant patients. The purpose of the study was to explore and identify factors that contribute to pharmacokinetic variability by developing and validating a population model using routine TDM data and routinely monitored biochemical and clinical parameters. The data obtained by routine monitoring of 38 patients over a period of one year from the sirolimus treatment initiation, were collected from patients' records. Population analysis was performed using the software NONMEM®. The validity of the model was tested by the internal and external validation techniques. The pharmacokinetic variability was partially explained with patient's age and liver function. CL/F was found to decrease with age. According to the developed model, sirolimus CL/F decreases by, in average, 37% in patients with aspartate aminotransferase (AST) greater than 37 IU/L. The internal and external validation confirmed the satisfactory prediction of the developed model. The population modeling of routinely monitored data allowed quantification of the age and liver function influence on sirolimus CL/F. According to the final model, patients with compromised liver function expressed via AST values require careful monitoring and dosing adjustments. Proven good predictive performance makes this model a useful tool in everyday clinical practice. © 2019 Bojana Golubović, Katarina Vučićević, Dragana Radivojević, Sandra Vezmar Kovačević, Milica Prostran, Branislava Miljković.

Due to wide intra-and inter-individual pharmacokinetic variability and narrow therapeutic index of sirolimus, the therapeutic drug monitoring (TDM) of sirolimus with detailed biochemical and clinical monitoring is necessary for dose individualization in kidney transplant patients. The purpose of the study was to explore and identify factors that contribute to pharmacokinetic variability by developing and validating a population model using routine TDM data and routinely monitored biochemical and clinical parameters. The data obtained by routine monitoring of 38 patients over a period of one year from the sirolimus treatment initiation, were collected from patients' records. Population analysis was performed using the software NONMEM®. The validity of the model was tested by the internal and external validation techniques. The pharmacokinetic variability was partially explained with patient's age and liver function. CL/F was found to decrease with age. According to the developed model, sirolimus CL/F decreases by, in average, 37% in patients with aspartate aminotransferase (AST) greater than 37 IU/L. The internal and external validation confirmed the satisfactory prediction of the developed model. The population modeling of routinely monitored data allowed quantification of the age and liver function influence on sirolimus CL/F. According to the final model, patients with compromised liver function expressed via AST values require careful monitoring and dosing adjustments. Proven good predictive performance makes this model a useful tool in everyday clinical practice. © 2019 Bojana Golubović, Katarina Vučićević, Dragana Radivojević, Sandra Vezmar Kovačević, Milica Prostran, Branislava Miljković.

Background/Aim. Selective serotonin reuptake inhibitors are the most commonly chosen antidepressants in patients with Parkinson's disease (PD). The aim of our study was to assess the influence of fluoxetine (Flu) on motor functions in patients with PD. Methods. In this prospective, controlled, open-label study, 18 patients with PD and mild depression [(10 ≤ Hamilton Rating Scale for Depression (HDRS) ≤ 23)] without dementia [(25 ≤ Mini-Mental State Examination (MMSE)] were treated with Flu. Both single and repeated dose effects of Flu were assessed on days 1-80. Plasma concentrations of Flu and norfluoxetine (NORFlu) were correlated with the results of selected motor function performance scores: The Unified Parkinsons Disease Rating Score (UPDRS), Finger Tapping Test (FTT) and Purdue Pegboard Test (PPT). Severity of PD, depression and dementia were evaluated using standard tests [(Hoehn and Yahr stages (HY), activity of daily living (ADL), UPDRS, HDRS, MMSE)]. Results. Steady-state for Flu/NORFlu was reached after 18 days of treatment. Such a plateau correlated with significant improvements in both scores of depression and Parkinson's disability (HDRS, UPDRS and ADL, respectively). In addition, FTT and PPT scores also increased until day 18, with further slight fluctuations around the plateau. Optimal motor performances correlated with Flu concentrations of approximately 60-110 μg/L. Conclusion. Flu (20 mg/day) significantly reduced depression in PD patients while it did not impair their motor performances. Because substantial placebo effects may arise in studies of PD and depression, large, prospective, randomized, placebo-controlled clinical trials are warranted.

Monitoring and optimization procedures improved high dose methotrexate (HDMTX) treatment outcomes. However, there are still some concerns regarding unexplained concentration variability. The objective of this study was to evaluate drug concentrations and associated variability factors in pediatric patients with acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL) on HDMTX. Fifty patients (aged 1–18 years), receiving in total 184 HDMTX cycles of 3 or 5 g/m2/24 h infusion, were included in the study. Comparisons of MTX concentrations and concentrations to dose ratio between two dosing groups were conducted by Mann-Whitney U test. Regression analysis was performed with transformed data to assess relationship between MTX concentration to dose ratio and patient characteristics, biochemical analysis and therapy data. Statistically significant difference in concentrations between 3 and 5 g/m2 dosing groups was detected only at 24 h after the start of infusion (p < 0.001), but not at 48 and 72 h (p > 0.05). There was no difference between dose-normalized concentrations. Regression analysis showed that 73.9% of variability in dependent variable can be explained by included variables: time since dose, creatinine clearance (CrCl), hemoglobin and certain concomitant therapy. Our results highlight the importance of not only renal function and concomitant therapy, but also hemoglobin in reducing the variation in MTX concentrations. Therefore, monitoring of aforementioned biochemical parameters during HDMTX is important not only to assess toxicity, but also in predicting their impact on drug level. © 2023 Taylor & Francis Group, LLC.

Purpose: The purpose of the study was to examine and describe adjunctive lamotrigine (LTG) pharmacokinetics in paediatric and young adult patients using a nonlinear mixed effects modelling (NONMEM) approach. Methods: The study included 53 patients (age range 3-35 years) who were concomitantly treated with carbamazepine (CBZ) and/or valproic acid (VPA). A total of 70 blood samples corresponding to trough levels were available for analysis. Data were modelled, and the final model was evaluated using NONMEM and auxiliary software tools. Results: The final LTG population model included the effects of concomitant drugs and patient's weight (WT) which stratified the population into three groups: ≤25 kg, >25 to <60 kg and ≥60 kg. Based on the final model, the estimated LTG oral clearance (CL/F) for a typical patient weighing ≤25 kg, >25 to <60 kg or ≥60 kg who was concomitantly treated with CBZ was estimated to be 3.28, 4.23, or 7.15 l/h, respectively. If a patient was concomitantly treated with CBZ + VPA, the CL/F decreased on average by 69.5 % relative to LTG + CBZ co-therapy. VPA was found to decrease the LTG CL/F by 87.6 % compared to co-therapy with only CBZ. Conclusion: The LTG population pharmacokinetic model developed in this study may be a reliable method for individualising the LTG dosing regimen in paediatric and young adult patients on combination therapy during therapeutic drug monitoring. © 2013 Springer-Verlag Berlin Heidelberg.

Purpose: The purpose of the study was to examine and describe adjunctive lamotrigine (LTG) pharmacokinetics in paediatric and young adult patients using a nonlinear mixed effects modelling (NONMEM) approach. Methods: The study included 53 patients (age range 3-35 years) who were concomitantly treated with carbamazepine (CBZ) and/or valproic acid (VPA). A total of 70 blood samples corresponding to trough levels were available for analysis. Data were modelled, and the final model was evaluated using NONMEM and auxiliary software tools. Results: The final LTG population model included the effects of concomitant drugs and patient's weight (WT) which stratified the population into three groups: ≤25 kg, >25 to <60 kg and ≥60 kg. Based on the final model, the estimated LTG oral clearance (CL/F) for a typical patient weighing ≤25 kg, >25 to <60 kg or ≥60 kg who was concomitantly treated with CBZ was estimated to be 3.28, 4.23, or 7.15 l/h, respectively. If a patient was concomitantly treated with CBZ + VPA, the CL/F decreased on average by 69.5 % relative to LTG + CBZ co-therapy. VPA was found to decrease the LTG CL/F by 87.6 % compared to co-therapy with only CBZ. Conclusion: The LTG population pharmacokinetic model developed in this study may be a reliable method for individualising the LTG dosing regimen in paediatric and young adult patients on combination therapy during therapeutic drug monitoring. © 2013 Springer-Verlag Berlin Heidelberg.

Background Drug–drug interactions represent one of the causes of adverse therapy outcomes through deteriorated efficacy or safety. However, the true extent of harm related to drug–drug interactions is not well established due to a lack of recognition and understanding. Objective The aim of this study was to investigate the association of potential drug–drug interactions with patients variables recorded at admission. Setting A cross-sectional correlation study was performed on the Cardiology ward of the University Clinical Hospital Center in Belgrade, Serbia. Method Data were retrospectively obtained from medical records and LexiInteract was used as the screening tool for potential drug–drug interactions. Main outcome measure Clinical and laboratory parameters recorded at the patients admission. Results A total of 351 patient records entered the analysis, with the mean age of 70 ± 10 years. The prevalence of potentially relevant drug–drug interactions was 61% (N = 213). After controlling for patient characteristics, nine potential drug–drug interactions were significantly associated with laboratory values outside the range and five potential drug–drug interactions with inadequate clinical parameter values. Potential drug–drug interactions were associated with abnormalities in blood count, metabolic parameters, electrolyte imbalance and renal function parameters. Association with inadequate control of systolic, diastolic blood pressure, as well as heart rhythm was also shown. Conclusion Drug–drug interactions were associated with patients clinical and laboratory findings. Our findings may assist in the identification of patients with increased likelihood of suboptimal therapy outcomes. Generating evidence through post-marketing drug–drug interactions research would lead to improvement in clinical decision-support systems, increased effectiveness and utilization in everyday clinical practice. © 2019, Springer Nature Switzerland AG.

Background Drug–drug interactions represent one of the causes of adverse therapy outcomes through deteriorated efficacy or safety. However, the true extent of harm related to drug–drug interactions is not well established due to a lack of recognition and understanding. Objective The aim of this study was to investigate the association of potential drug–drug interactions with patients variables recorded at admission. Setting A cross-sectional correlation study was performed on the Cardiology ward of the University Clinical Hospital Center in Belgrade, Serbia. Method Data were retrospectively obtained from medical records and LexiInteract was used as the screening tool for potential drug–drug interactions. Main outcome measure Clinical and laboratory parameters recorded at the patients admission. Results A total of 351 patient records entered the analysis, with the mean age of 70 ± 10 years. The prevalence of potentially relevant drug–drug interactions was 61% (N = 213). After controlling for patient characteristics, nine potential drug–drug interactions were significantly associated with laboratory values outside the range and five potential drug–drug interactions with inadequate clinical parameter values. Potential drug–drug interactions were associated with abnormalities in blood count, metabolic parameters, electrolyte imbalance and renal function parameters. Association with inadequate control of systolic, diastolic blood pressure, as well as heart rhythm was also shown. Conclusion Drug–drug interactions were associated with patients clinical and laboratory findings. Our findings may assist in the identification of patients with increased likelihood of suboptimal therapy outcomes. Generating evidence through post-marketing drug–drug interactions research would lead to improvement in clinical decision-support systems, increased effectiveness and utilization in everyday clinical practice. © 2019, Springer Nature Switzerland AG.

Background In the last 30 years, activities of hospital pharmacists have gone through significant changes. Pharmacists are increasingly involved in patient care. Objectives To explore drug-related and logistic problems, interventions, and their outcomes during routine everyday work of hospital pharmacists. Setting Institute for physical medicine and rehabilitation, Banja Luka, Bosnia and Herzegovina. Methods In the period of January 2013–October 2015 a prospective observational study was performed. Medical doctors, nurses, therapists, and patients addressed pharmacists, face-to-face or by telephone, with drug-related problems (DRPs) and/or logistic issues. Main outcome measure Type of DRP or logistic issue, intervention, outcome, initiator and time spent for solving the problem were documented for each consultation. Results Out of 1515 interventions, 48.8% were aimed at solving DRPs. The most common DRPs were the recommendation of a drug or dose and need for additional information about drugs. Drug price and supply were the most prevalent logistic issues. DRPs were more frequently initiated by medical doctors and required more time to solve the problem compared to logistic issues (Mann–Whitney U test, p ≤ 0.001, respectively). The acceptance rate of interventions to solve DRPs (83.7%) was lower compared to logistic issues (95.2%; p ≤ 0.001). Conclusions Hospital pharmacists were faced with an approximately equal number of DRPs and logistic issues during their routine everyday work. The overall acceptance rate of pharmacists’ interventions was high, and the results of our study indicate that there is a need for more involvement of hospital pharmacists in Bosnia and Herzegovina in clinical activities. Impact on practice. © 2017, Springer International Publishing.

Background In the last 30 years, activities of hospital pharmacists have gone through significant changes. Pharmacists are increasingly involved in patient care. Objectives To explore drug-related and logistic problems, interventions, and their outcomes during routine everyday work of hospital pharmacists. Setting Institute for physical medicine and rehabilitation, Banja Luka, Bosnia and Herzegovina. Methods In the period of January 2013–October 2015 a prospective observational study was performed. Medical doctors, nurses, therapists, and patients addressed pharmacists, face-to-face or by telephone, with drug-related problems (DRPs) and/or logistic issues. Main outcome measure Type of DRP or logistic issue, intervention, outcome, initiator and time spent for solving the problem were documented for each consultation. Results Out of 1515 interventions, 48.8% were aimed at solving DRPs. The most common DRPs were the recommendation of a drug or dose and need for additional information about drugs. Drug price and supply were the most prevalent logistic issues. DRPs were more frequently initiated by medical doctors and required more time to solve the problem compared to logistic issues (Mann–Whitney U test, p ≤ 0.001, respectively). The acceptance rate of interventions to solve DRPs (83.7%) was lower compared to logistic issues (95.2%; p ≤ 0.001). Conclusions Hospital pharmacists were faced with an approximately equal number of DRPs and logistic issues during their routine everyday work. The overall acceptance rate of pharmacists’ interventions was high, and the results of our study indicate that there is a need for more involvement of hospital pharmacists in Bosnia and Herzegovina in clinical activities. Impact on practice. © 2017, Springer International Publishing.