Controlled, multidose, pharmacokinetic evaluation of two extended-release carbamazepine formulations (Carbatrol and Tegretol-XR).
A major limitation of conventional carbamazepine (CBZ) formulations is their pharmacokinetics, which typically require q.i.d. dosing. Two extended-release formulations of CBZ have been developed recently to support b.i.d. dosing. One, Carbatrol (CBTL) uses immediate-, extended-, and enteric-release beads in a capsule. The other, Tegretol-XR (TXR), uses an osmotic pump (Oros tablet). To our knowledge, this is the first head-to-head comparison of the multidose pharmacokinetics of these two new formulations. The objective of the study was to evaluate the pharmacokinetics of carbamazepine (CBZ) and CBZ-10,11-expoxide (CBZ-E) after multidose b.i.d. dosing with CBTL or TXR. In this randomized, crossover study, 15 normal healthy adults received 400 mg of each formulation b.i.d. for 5 days. Blood samples for CBZ and CBZ-E analysis were obtained prior to morning doses on all days and hourly for 12 h after the Day 5 dose. There was a minimum interperiod washout of 9 days. For CBTL and TXR, the key CBZ pharmacokinetic measures of area under the curve of concentration versus time (AUC(0-tau)), maximum concentration (Cmax), and minimum concentration (Cmin) were bioequivalent. The ratio for CBTL-to-TXR was 98% (90% confidence intervals, 92-104%), 107% (96-118%), and 96% (89-104%), respectively. Similar ratios were also observed for CBZ-E: 102% (97-107%), 99% (92-107%), and 93% (83-109%), respectively. In conclusion, CBTL b.i.d. and TXR b.i.d. were bioequivalent in their pharmacokinetic parameters for CBZ and CBZ-E after 5 days of dosing.
Stevens
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Phoenix International Life Sciences, Inc., Cincinnati, Ohio 45224, USA.
Limsakun
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Evans
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Mason
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DH
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D001682:Biological Availability; D002220:Carbamazepine / Q000097:blood*; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009995:Osmosis
D003692:Delayed-Action Preparations; D002220:Carbamazepine