Carbamazepine Differentially Affects the Pharmacokinetics of Fexofenadine Enantiomers.
Summary of "Carbamazepine Differentially Affects the Pharmacokinetics of Fexofenadine Enantiomers."
What is already known about this subject- We have shown that P-gp inhibitors such as itraconazole and verapamil significantly increase the plasma concentrations of fexofenadine enantiomers, and their effects are greater for (S)-fexofenadine compared to the (R)-enantiomer. These mechanisms are likely to be due to inhibition of intestinal P-gp because the t(1/2) and CL(renal) were constant during the study, and suggest that intestinal P-gp plays an important role in pharmacokinetics of fexofenadine enantiomers. To date, there is no information whether P-gp inducer carbamazepine affects the pharmacokinetics of either fexofenadine enantiomer. What this study adds- This study indicates that the stereoselectivity of fexofenadine pharmacokinetics may be influenced by carbamazepine primarily due to the induction of intestinal P-gp, and this affect may be greater for (S)-fexofenadine compared to (R)-fexofenadine. However, since the inductive effect of carbamazepine did not eliminate the difference between the pharmacokinetics of the fexofenadine enantiomers, it is likely that other transporters, including OATP2B1 and MRP2, also contribute to the stereoselective pharmacokinetics of fexofenadine.
ABSTRACT:
Aim: This study was to characterize the impact of the P-glycoprotein (P-gp) inducer carbamazepine on fexofenadine enantiomer pharmacokinetics. Methods: Twelve healthy volunteers initially received a 60 mg dose of fexofenadine alone. Subsequently, a 100 mg dose of carbamazepine was administered 3 times daily (300 mg/day), and on day 7, fexofenadine was co-administered. Results: Carbamazepine significantly decreased the area under the plasma concentration-time curve and the amount excreted into the urine of (S)- and (R)-fexofenadine. The P-gp inducer showed a greater effect on pharmacokinetic parameters of (S)-fexofenadine. Conclusion: This study indicates that carbamazepine may alter the pharmacokinetics of fexofenadine enantiomers.
Affiliation
Department of Hospital Pharmacy, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan; Department of Pharmacy, Akita University Hospital, Akita, Japan; Department of Neuropsychiatry, Hirosaki University School of Medici
Journal Details
This article was published in the following journal.
Name: British journal of clinical pharmacology
ISSN: 1365-2125
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/21950458
- DOI: http://dx.doi.org/10.1111/j.1365-2125.2011.04106.x
Medical and Biotech [MESH] Definitions
Carbamazepine
An anticonvulsant used to control grand mal and psychomotor or focal seizures. Its mode of action is not fully understood, but some of its actions resemble those of PHENYTOIN; although there is little chemical resemblance between the two compounds, their three-dimensional structure is similar.
Adjuvants, Pharmaceutic
Agents that aid or increase the action of the principle drug (DRUG SYNERGISM) or that affect the absorption, mechanism of action, metabolism, or excretion of the primary drug (PHARMACOKINETICS) in such a way as to enhance its effects.
Discrimination Learning
Learning that is manifested in the ability to respond differentially to various stimuli.
Insulator Elements
Nucleic acid regulatory sequences that limit or oppose the action of ENHANCER ELEMENTS and define the boundary between differentially regulated gene loci.
Euchromatin
Chromosome regions that are loosely packaged and more accessible to RNA polymerases than HETEROCHROMATIN. These regions also stain differentially in CHROMOSOME BANDING preparations.
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