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PII‐65
Author(s) -
Marino S. E.,
Cloyd J. C.,
Brundage R. C.,
Birnbaum A. K.,
Conway J. M.,
Musib L. C.,
Ramsay R. E.,
Pennell P. B.,
White J. R.,
Leppik I. E.,
Rarick J. O.,
Mishra U. R.,
Beattie J.
Publication year - 2006
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2005.12.190
Subject(s) - pharmacokinetics , bioavailability , volume of distribution , carbamazepine , pharmacology , clinical pharmacology , half life , distribution (mathematics) , medicine , oral administration , morning , chemistry , mathematics , epilepsy , mathematical analysis , psychiatry
BACKGROUND Carbamazepine (CBZ) is among the most widely prescribed antiepileptic drugs. There are no reports describing the absolute bioavailability, distribution volume, and half life of CBZ in patients at steady state. We have developed an investigational, intravenous, stable‐labeled (SL) CBZ formulation in order to rigorously characterize steady‐state CBZ pharmacokinetics without interrupting therapy. METHODS Patients were given a single 100 mg IV infusion of SL‐CBZ as part of their morning dose. The remainder of the dose was given orally. Blood samples were collected just prior to and up to 96 hours after drug administration. CBZ and SL‐CBZ were measured in plasma using LC‐MS. Concentration‐time data were analyzed using a noncompartmental approach with WinNonLin 4.0. RESULTS Data for 56 patients (25 F, 31 M; 19–82 yrs; daily dose range: 200–2400mg, formulations included immediate and extended release preparations) were analyzed. Pharmacokinetic parameters (mean±sd) are: bioavailability = 0.77±.21, distribution volume = 1.36±0.37 L/kg, clearance = 0.04±.01 L/hr/kg, and elimination half‐life = 23.9±7.4 hrs. CONCLUSION Among the subjects, CBZ bioavailability and distribution volume vary as much as twofold. Elimination half life is approximately one day and appears to be longer than previous estimates. Further analysis of the data will permit a comprehensive characterization of the effects of age, gender, and genotype on steady‐state CBZ PK in patients. Clinical Pharmacology & Therapeutics (2005) 79 , P53–P53; doi: 10.1016/j.clpt.2005.12.190