Pharmacokinetics of the monohydroxy derivative of oxcarbazepine and its
enantiomers after a single intravenous dose given as racemate compared with a
single oral dose of oxcarbazepine.
Author(s): Flesch G, Czendlik C, Renard D, Lloyd P.
Affiliation(s): Modeling & Simulation, WSJ-027.6.69, Novartis Limited, CH-4002 Basel,
Switzerland. gerard_jp.flesch@novartis.com
Publication date & source: 2011, Drug Metab Dispos. , 39(6):1103-10
Oxcarbazepine (OXC) is an antiepileptic drug. In humans, OXC is metabolized via
reduction and conjugation. Monohydroxy derivative of OXC (MHD) is the major
pharmacologically active component after OXC ingestion. This study was performed
to characterize the disposition of the two enantiomers of MHD after oral and
intravenous administration and to estimate the bioavailability of MHD after a
single oral dose administration of OXC compared to a single intravenous
administration of MHD. The study was performed in two parts. In a first pilot
study, three intravenous doses were given in an ascending manner (150, 200, and
250 mg of MHD; one subject per dose level) to assess the safety, tolerability,
and basic pharmacokinetics. Part two was an open, single-center, randomized,
two-way crossover, single-dose trial in 12 healthy adult subjects (n = 6 males
and n = 6 females) given OXC orally (one film-coated 300-mg tablet of OXC) and
MHD intravenously (250 mg infused over 30 min). Concentrations of OXC and its
metabolites were measured by means of high-performance liquid chromatography
methods. OXC given as a tablet is completely absorbed in man under fasting
conditions. When MHD is given intravenously, (S)-MHD predominates as free
compound in plasma. When OXC is administered orally, the ratio of the
area-under-the-curve values of (S)-MHD over (R)-MHD equals 3.8, indicating an
enantioselective reduction of the prochiral carbonyl group of OXC.
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