Browsing by Author "Prostran, M.Š. (7004009031)"

What is known and Objective: Lamotrigine metabolism may be substantially altered with concomitant administration of valproic acid and/or carbamazepine. Such alterations may require the adjustment of lamotrigine dose to ensure optimal treatment efficacy and safety. Methods: The extent of lamotrigine interactions was investigated dependent on age, gender, weight and dose of concomitant carbamazepine and/or valproic acid in 65 patients with epilepsy. Lamotrigine plasma steady-state oral clearance (CLss/F) and area under the curve (AUCss) were calculated from the dose of drug, average steady-state concentration (Css) and interval of administration. Multiple regression analysis was used for the identification and quantification of factors that influenced lamotrigine pharmacokinetics. Results and Discussion: Age and dose of carbamazepine and valproic acid had significant influence on lamotrigine CLss/F and AUCss. Carbamazepine was associated with a dose-dependent increase and valproic acid with a dose-dependent decrease of lamotrigine metabolism rate. The effect of carbamazepine was more pronounced. Younger patients were expected to metabolize lamotrigine more rapidly whereas overweight patients may be less susceptible to interactions. Gender had no influence on lamotrigine pharmacokinetics. What is new and Conclusion: The efficacy and safety of lamotrigine may be altered by concomitant administration of carbamazepine and valproic acid. The models developed may be useful for estimating doses of lamotrigine for individual patients to minimize clinically significant interactions. Therapeutic monitoring is advisable when those drugs are used concomitantly. © 2012 Blackwell Publishing Ltd.

What is known and Objective: Lamotrigine metabolism may be substantially altered with concomitant administration of valproic acid and/or carbamazepine. Such alterations may require the adjustment of lamotrigine dose to ensure optimal treatment efficacy and safety. Methods: The extent of lamotrigine interactions was investigated dependent on age, gender, weight and dose of concomitant carbamazepine and/or valproic acid in 65 patients with epilepsy. Lamotrigine plasma steady-state oral clearance (CLss/F) and area under the curve (AUCss) were calculated from the dose of drug, average steady-state concentration (Css) and interval of administration. Multiple regression analysis was used for the identification and quantification of factors that influenced lamotrigine pharmacokinetics. Results and Discussion: Age and dose of carbamazepine and valproic acid had significant influence on lamotrigine CLss/F and AUCss. Carbamazepine was associated with a dose-dependent increase and valproic acid with a dose-dependent decrease of lamotrigine metabolism rate. The effect of carbamazepine was more pronounced. Younger patients were expected to metabolize lamotrigine more rapidly whereas overweight patients may be less susceptible to interactions. Gender had no influence on lamotrigine pharmacokinetics. What is new and Conclusion: The efficacy and safety of lamotrigine may be altered by concomitant administration of carbamazepine and valproic acid. The models developed may be useful for estimating doses of lamotrigine for individual patients to minimize clinically significant interactions. Therapeutic monitoring is advisable when those drugs are used concomitantly. © 2012 Blackwell Publishing Ltd.

The mechanisms of the analgesic action of carbamazepine and oxcarbazepine, in particular the role of opioid receptors, have not been established precisely. The systemic effects of naloxone, an opioid receptor antagonist, on the antihyperalgesic effects of carbamazepine and oxcarbazepine were examined in the model of inflammatory hyperalgesia induced by the intraplantar (i.pl.) administration of concanavaline A (Con A, 0.8 mglpaw) into the rat hind paw. Naloxone (3 mglkg; i.p.) did not alter the antihyperalgesic effects of either carbamazepine or oxcarbazepine. These results indicate that the opioid system of pain modulation does not play a significant role in the antihyperalgesic effects of carbamazepine and oxcarbazepine. © 2007 Prous Science. All rights reserved.

The mechanisms of the analgesic action of carbamazepine and oxcarbazepine, in particular the role of opioid receptors, have not been established precisely. The systemic effects of naloxone, an opioid receptor antagonist, on the antihyperalgesic effects of carbamazepine and oxcarbazepine were examined in the model of inflammatory hyperalgesia induced by the intraplantar (i.pl.) administration of concanavaline A (Con A, 0.8 mglpaw) into the rat hind paw. Naloxone (3 mglkg; i.p.) did not alter the antihyperalgesic effects of either carbamazepine or oxcarbazepine. These results indicate that the opioid system of pain modulation does not play a significant role in the antihyperalgesic effects of carbamazepine and oxcarbazepine. © 2007 Prous Science. All rights reserved.