Steady-state carbamazepine pharmacokinetics following oral and stable-labeled intravenous administration in epilepsy patients: effects of race and sex
| Autor: | Cynthia R. Gross, James R. White, Ilo E. Leppik, Richard C. Brundage, Susan E. Marino, Jeannine M. Conway, Usha Mishra, James C. Cloyd, L. C. Musib, John O. Rarick, R. E. Ramsay, Angela K. Birnbaum, Page B. Pennell |
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| Rok vydání: | 2012 |
| Předmět: |
Drug
Adult Male media_common.quotation_subject Chemistry Pharmaceutical Administration Oral Biological Availability Pharmacology 030226 pharmacology & pharmacy Article 03 medical and health sciences Epilepsy 0302 clinical medicine Sex Factors Pharmacokinetics Medicine Humans Pharmacology (medical) In patient Dosing steady-state Infusions Intravenous media_common business.industry Half-life Carbamazepine medicine.disease 3. Good health Anticonvulsants Female Steady state (chemistry) stable-labeled isotope business pharmacokinetics 030217 neurology & neurosurgery medicine.drug Half-Life |
| Zdroj: | Clinical pharmacology and therapeutics |
| ISSN: | 1532-6535 |
| Popis: | Carbamazepine is a widely prescribed antiepileptic drug. Owing to the lack of an intravenous formulation, its absolute bioavailability, absolute clearance, and half-life in patients at steady state have not been determined. We developed an intravenous, stable-labeled (SL) formulation in order to characterize carbamazepine pharmacokinetics in patients. Ninety-two patients received a 100-mg infusion of SL-carbamazepine as part of their morning dose. Blood samples were collected up to 96 hours after drug administration. Plasma drug concentrations were measured with liquid chromatography-mass spectrometry, and concentration-time data were analyzed using a noncompartmental approach. Absolute clearance (l/hr/kg) was significantly lower in men (0.039 ± 0.017) than in women (0.049 ± 0.018; P = 0.007) and in African Americans (0.039 ± 0.017) when compared with Caucasians (0.048 ± 0.018; P = 0.019). Half-life was significantly longer in men than in women as well as in African Americans as compared with Caucasians. The absolute bioavailability was 0.78. Sex and racial differences in clearance may contribute to variable dosing requirements and clinical response. |
| Databáze: | OpenAIRE |
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