Pantoprazole does not interact with the pharmacokinetics of carbamazepine.
OBJECTIVE
Pantoprazole is a H+/K+-ATPase inhibitor with a minimized potential of interaction with the cytochrome P450 system. Imidazole derivatives such as cimetidine and omeprazole have been shown to markedly interact with carbamazepine, a major anticonvulsant with a narrow therapeutic range. Therefore, the influence of steady-state pantoprazole on the pharmacokinetics of carbamazepine was investigated.


METHODS
N = 20 healthy volunteers (12 male/8 female) completed a double-blind, placebo-controlled, randomized crossover study. During the test period they received 40 mg pantoprazole p.o. once daily for 11 days and concomitantly a single oral dose of 400 mg carbamazepine on day 5. In the reference period placebo was administered instead of pantoprazole.


RESULTS
Serum concentrations of carbamazepine and its active metabolite carbamazepine-10,11-epoxide were measured until day 11. Geometric means of AUC (extent characteristic) and Cmax/AUC (rate characteristic) of carbamazepine were 292 and 287 mgxh/l, and 0.0150 and 0.0144 l/h (reference and test), respectively. Point estimates and 90% confidence intervals of the ratios were 0.98 (0.95, 1.01) for AUC, and 0.96 (0.92, 1.00) for Cmax/AUC, respectively. Since the 90% confidence intervals of the primary characteristics, AUC and Cmax/AUC were entirely within the predefined equivalence range of 0.80 - 1.25, lack of interaction of pantoprazole with the pharmacokinetics of carbamazepine was demonstrated. Equivalence was also demonstrated for carbamazepine-10,11-epoxide using the characteristics AUC and Cmax.


CONCLUSIONS
No dose adjustment of carbamazepine is therefore required during concomitant treatment with pantoprazole.
Huber
R
R
Byk Gulden Pharmaceuticals, Konstanz, Germany.
Bliesath
H
H
Hartmann
M
M
Steinijans
V W
VW
Koch
H
H
Mascher
H
H
Wurst
W
W
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001562:Benzimidazoles / Q000009:adverse effects / Q000494:pharmacology*; D001711:Biotransformation; D002220:Carbamazepine / Q000009:adverse effects / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D009853:Omeprazole / Q000031:analogs & derivatives; D000077402:Pantoprazole; D054328:Proton Pump Inhibitors; D013454:Sulfoxides / Q000009:adverse effects / Q000494:pharmacology*
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000927:Anticonvulsants; D001562:Benzimidazoles; D004791:Enzyme Inhibitors; D054328:Proton Pump Inhibitors; D013454:Sulfoxides; D002220:Carbamazepine; D000077402:Pantoprazole; D009853:Omeprazole