TITLE

Steady-State Carbamazepine Pharmacokinetics Following Oral and Stable-Labeled Intravenous Administration in Epilepsy Patients: Effects of Race and Sex

AUTHOR(S)

Marino, S E; Birnbaum, A K; Leppik, I E; Conway, J M; Musib, L C; Brundage, R C; Ramsay, R E; Pennell, P B; White, J R; Gross, C R; Rarick, J O; Mishra, U; Cloyd, J C

PUB. DATE

March 2012

SOURCE

Clinical Pharmacology & Therapeutics;Mar2012, Vol. 91 Issue 3, p483

SOURCE TYPE

Academic Journal

DOC. TYPE

Article

ABSTRACT

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.

ACCESSION #

71818565

Tags: CARBAMAZEPINE;  PHARMACOKINETICS;  DRUG bioavailability;  INTRAVENOUS therapy;  EPILEPTICS -- Medical care;  AFRICAN Americans;  CAUCASIAN race

 

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