Browsing by Author "Pokrajac, M. (6701564186)"

The cerebrospinal fluid (CSF) and plasma pharmacokinetics of phenobarbital were studied after intravenous administration to 5 epileptic patients with convulsive status epilepticus and 6 seizure-free patients with newly diagnosed epilepsy. Phenobarbital (15 mg/kg) was infused at a rate of 100 mg/min. Plasma was collected prior to and throughout 24 hours after drug administration. The CSF samples were obtained by lumbar puncture 2 hours after the institution of phenobarbital infusion. Phenobarbital concentrations in plasma and the CSF were measured by reverse-phase liquid chromatography. The plasma values of pharmacokinetic variables of distribution and elimination did not differ between the groups. Slightly lower phenobarbital concentrations in the group of patients experiencing status epilepticus compared with seizure-free epileptic patients during the first hours after drug administration and the resultant elevated value of the rate constant distribution (α) did not reach statistical significance, probably due to the small number of participants in the study. Phenobarbital concentrations were approximately 40% higher in the CSF of epileptic patients with status epilepticus compared with nonconvulsing subjects. The rate constant of phenobarbital distribution in the CSF (the ratio of the CSF concentration of the drug at time t1 and the area under the plasma concentration-time curve up to t(l)) in epileptic patients with status epilepticus exceeded that in seizure-free patients (0.29 ± 0.06 h-1 vs 0.19 ± 0.05 h-1, p < 0.05). The study demonstrated statistically significantly higher phenobarbital concentrations and more rapid appearance of phenobarbital in the CSF of epileptic patients with status epilepticus compared with nonconvulsing patients with epilepsy. The alteration in the pharmacokinetics of phenobarbitone in patients experiencing status epilepticus reported here additionally supports the reported efficacy of intravenous phenobarbital in the treatment neurological disorder.

Although many attempts have been made, to date no convincing evidence exists of a relationship between plasma concentrations of amitriptyline (AT), its active metabolite nortriptyline (NT) and clinical response. Fifteen patients with primary depression (according to DSM-IV) were divided in two groups according to given doses: (I) 6 patients received 3 x 50 mg of AT daily; and (II) 9 patients received 3 x 25 mg of AT daily, for 6 weeks. The clinical status was determined with Hamilton Depression Rating Scale. Both investigated doses were therapeutically effective. AT and NT plasma concentrations were assayed by high performance liquid chromatography. Following administration of 3 x 50 mg of AT daily, the correlation of concentrations of AT, NT, total AT + NT and clinical response were r(AT) = -0.702 (P < 0.1), rNT = -0.761 (P < 0.1), r(AT+NT) = -0.741 (P < 0.1). The linear and very high correlation were also present with concentrations of AT, NT, total AT + NT and clinical response in depressive patients on 3 x 25 mg AT daily: r(AT) = -0.785 (P < 0.02), r(NT) = -0.811 (P < 0.01), r(AT+NT) = -0.848 (P < 0.01). Our results support a high correlation between AT/NT plasma concentrations and clinical response indicating that therapeutic monitoring of AT and its metabolite, NT, can provide eventual clinical response.

Although many attempts have been made, to date no convincing evidence exists of a relationship between plasma concentrations of amitriptyline (AT), its active metabolite nortriptyline (NT) and clinical response. Fifteen patients with primary depression (according to DSM-IV) were divided in two groups according to given doses: (I) 6 patients received 3 x 50 mg of AT daily; and (II) 9 patients received 3 x 25 mg of AT daily, for 6 weeks. The clinical status was determined with Hamilton Depression Rating Scale. Both investigated doses were therapeutically effective. AT and NT plasma concentrations were assayed by high performance liquid chromatography. Following administration of 3 x 50 mg of AT daily, the correlation of concentrations of AT, NT, total AT + NT and clinical response were r(AT) = -0.702 (P < 0.1), rNT = -0.761 (P < 0.1), r(AT+NT) = -0.741 (P < 0.1). The linear and very high correlation were also present with concentrations of AT, NT, total AT + NT and clinical response in depressive patients on 3 x 25 mg AT daily: r(AT) = -0.785 (P < 0.02), r(NT) = -0.811 (P < 0.01), r(AT+NT) = -0.848 (P < 0.01). Our results support a high correlation between AT/NT plasma concentrations and clinical response indicating that therapeutic monitoring of AT and its metabolite, NT, can provide eventual clinical response.

[No abstract available]

[No abstract available]

The pharmacokinetics of theophylline was investigated in five hyperthyroid, five hypothyroid, and five euthyroid patients, all with chronic obstructive pulmonary disease. Wide individual variability was found in theophylline kinetics, but the rate of elimination of theophylline was significantly higher in hyperthyroid, and lower in hypothyroid patients than in the euthyroid patients (kel=0.155, 0.060 and 0.107 h-1, respectively). The values for clearance and volume of distribution were not consistently changed compared with those in the euthyroid group, although all the parameters except AUC were significantly different in hyperthyroid and hypothyroid patients. There was a positive correlation between both thyroxine and triiodothyronine serum concentrations and total body clearance of theophylline (r=0.795 and r=0.791, respectively). It is concluded that in spite of the wide interindividual variability and the relatively small differences in the pharmacokinetics of theophylline in thyroid dysfunction compared with the euthyroid status, these differences have to be considered in certain clinical situations, as they may require changes in the therapeutic regimen for administration of theophylline in hyperthyroid or hypothyroid patients. © 1987 Springer-Verlag.

The pharmacokinetics of theophylline was investigated in five hyperthyroid, five hypothyroid, and five euthyroid patients, all with chronic obstructive pulmonary disease. Wide individual variability was found in theophylline kinetics, but the rate of elimination of theophylline was significantly higher in hyperthyroid, and lower in hypothyroid patients than in the euthyroid patients (kel=0.155, 0.060 and 0.107 h-1, respectively). The values for clearance and volume of distribution were not consistently changed compared with those in the euthyroid group, although all the parameters except AUC were significantly different in hyperthyroid and hypothyroid patients. There was a positive correlation between both thyroxine and triiodothyronine serum concentrations and total body clearance of theophylline (r=0.795 and r=0.791, respectively). It is concluded that in spite of the wide interindividual variability and the relatively small differences in the pharmacokinetics of theophylline in thyroid dysfunction compared with the euthyroid status, these differences have to be considered in certain clinical situations, as they may require changes in the therapeutic regimen for administration of theophylline in hyperthyroid or hypothyroid patients. © 1987 Springer-Verlag.

Objectives. - To determine prevalence and characteristics of menstrually related migraine and nonmigraine headache in female students of Belgrade University. Method. - A questionnaire was administered to female students during randomly selected classes of the Schools of Medicine and Pharmacy. Diagnoses were assigned according to the criteria of the International Headache Society and MacGregor's stricter definition of "menstrual" migraine. Results. - Of 1943 female students (18 to 28 years old), 1298 (66.8%) had primary headaches. Among 1298 students with headache, 245 (12.6%) had migraine and 1053 (54.2%) had nonmigraine headache. The prevalence rates of migraine versus nonmigraine headache in relation to the menstrual cycle were: premenstrual, 0.9% versus 4.4%; menstrual, 1.5% versus 1.5%; menstrually associated, 6.1% versus 10.1%; menstrually unchanged, 2.7% versus 19.2%; and menstrually unrelated, 1.4% versus 18.9%. Female students with migraine had menstrually related attacks more frequently than students with nonmigraine headache (67.7% versus 29.5%). This difference was most prominent among students with menstrual migraine compared with students with menstrual nonmigraine headache (12.2% versus 2.7%). Exacerbation of migraine during menstruation was slightly more severe and more complex than exacerbation of nonmigraine headache. Female students with migraine versus nonmigraine headache did not differ significantly in age, age at onset of menarche, or age at onset of headache. Female students with migraine were significantly more likely to report a positive family history for migraine and menstrual migraine, severe attacks, reduced work activity, and aura. Conclusion. - The results obtained are in accord with the prevailing opinion that there is a relationship between migraine and female sex hormones, and suggest that women with nonmigraine headache are also susceptible to hormonal fluctuations.

Objectives. - To determine prevalence and characteristics of menstrually related migraine and nonmigraine headache in female students of Belgrade University. Method. - A questionnaire was administered to female students during randomly selected classes of the Schools of Medicine and Pharmacy. Diagnoses were assigned according to the criteria of the International Headache Society and MacGregor's stricter definition of "menstrual" migraine. Results. - Of 1943 female students (18 to 28 years old), 1298 (66.8%) had primary headaches. Among 1298 students with headache, 245 (12.6%) had migraine and 1053 (54.2%) had nonmigraine headache. The prevalence rates of migraine versus nonmigraine headache in relation to the menstrual cycle were: premenstrual, 0.9% versus 4.4%; menstrual, 1.5% versus 1.5%; menstrually associated, 6.1% versus 10.1%; menstrually unchanged, 2.7% versus 19.2%; and menstrually unrelated, 1.4% versus 18.9%. Female students with migraine had menstrually related attacks more frequently than students with nonmigraine headache (67.7% versus 29.5%). This difference was most prominent among students with menstrual migraine compared with students with menstrual nonmigraine headache (12.2% versus 2.7%). Exacerbation of migraine during menstruation was slightly more severe and more complex than exacerbation of nonmigraine headache. Female students with migraine versus nonmigraine headache did not differ significantly in age, age at onset of menarche, or age at onset of headache. Female students with migraine were significantly more likely to report a positive family history for migraine and menstrual migraine, severe attacks, reduced work activity, and aura. Conclusion. - The results obtained are in accord with the prevailing opinion that there is a relationship between migraine and female sex hormones, and suggest that women with nonmigraine headache are also susceptible to hormonal fluctuations.

The influence of lithium on fluvoxamine therapeutic efficacy plasma concentrations and pharmacokinetics was studied in 12 depressed inpatients. Six patients were on fluvoxamine monotherapy and six were on combined fluvoxamine-lithium therapy. The treatment response was determined using 17-item Hamilton Rating Scale for Depression. Blood samples were collected during 48 h after a single dose administration of 100 mg fluvoxamine, and five times at steady state after repeated doses of 100 mg fluvoxamine per day. The evaluation of 17-item Hamilton Rating Scale for Depression Scores showed a significant clinical improvement 2 and 4 weeks after the beginning of the therapy in both groups (p < 0.01). However, 2 weeks after the administration of the drug(s) had started, significant differences (p < 0.05) in efficacy between the two treatments in favour of the fluvoxamine-lithium combination were found. Plasma concentrations of fluvoxamine were measured by high-performance liquid chromatography The comparison of the measured concentrations of fluvoxamine showed a similar course of the plasma concentration-time curves in both groups of patients. Pharmacokinetic parameters of fluvoxamine did not show any significant difference on the comparison between the groups. According to the results from this study it is evident that lithium does not affect plasma concentrations and pharmacokinetics of fluvoxamine in depressed patients on concomitant treatment with these two drugs. However, the effect achieved with the combination was better.

As part of an investigation of phenobarbital (PB) pharmacokinetics in patients with status epilepticus (SE), urinary excretion of PB and its main metabolite, hydroxyphenobarbital (HPB), was studied in patients who had an episode of SE, as well as in non-convulsing ones. Eleven in-patients were studied: (group 1) five patients (4 M + 1 F; 48 ± 28 years old; 64 ± 6 kg body weight; mean ± SD) with convulsive status epilepticus, and (group 2) six patients (5 M + 1 F; 37 ± 13 years old; 71 ± 15 kg body weight) with epilepsy, seizure-free at the moment of PB administration and without established anti-epileptic therapy. All subjects received a single intravenous dose of PB (15 mg/kg) at a rate of 100 mg/min. PB and HPB concentrations were measured by high performance liquid chromatography with UV detection at 220 nm in urine samples collected throughout 24 h. The comparison of pharmacokinetic parameters of urinary excretion of PB and HPB showed a statistically significant difference in the values of recovery of HPB and total barbiturate (higher values in the patients with SE) in 24 h urine. Differences in the excretion of PB between the two groups of patients - higher values in the patients who had had an episode of SE, and in urine flow - slightly elevated volumes in the same group, failed to reach statistical significance, probably due to the small number of participants in the study.

As part of an investigation of phenobarbital (PB) pharmacokinetics in patients with status epilepticus (SE), urinary excretion of PB and its main metabolite, hydroxyphenobarbital (HPB), was studied in patients who had an episode of SE, as well as in non-convulsing ones. Eleven in-patients were studied: (group 1) five patients (4 M + 1 F; 48 ± 28 years old; 64 ± 6 kg body weight; mean ± SD) with convulsive status epilepticus, and (group 2) six patients (5 M + 1 F; 37 ± 13 years old; 71 ± 15 kg body weight) with epilepsy, seizure-free at the moment of PB administration and without established anti-epileptic therapy. All subjects received a single intravenous dose of PB (15 mg/kg) at a rate of 100 mg/min. PB and HPB concentrations were measured by high performance liquid chromatography with UV detection at 220 nm in urine samples collected throughout 24 h. The comparison of pharmacokinetic parameters of urinary excretion of PB and HPB showed a statistically significant difference in the values of recovery of HPB and total barbiturate (higher values in the patients with SE) in 24 h urine. Differences in the excretion of PB between the two groups of patients - higher values in the patients who had had an episode of SE, and in urine flow - slightly elevated volumes in the same group, failed to reach statistical significance, probably due to the small number of participants in the study.