Decrease in the oral bioavailability of dabigatran etexilate after co-medication with rifampicin.

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Hartter S, Koenen-Bergmann M, Sharma A, Nehmiz G, Lemke U, Timmer W, Reilly PA

Decrease in the oral bioavailability of dabigatran etexilate after co-medication with rifampicin.

Br J Clin Pharmacol. 2012 Sep;74(3):490-500. doi: 10.1111/j.1365-2125.2012.04218.x.

PubMed ID

22348256 [ View in PubMed

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Abstract

AIMS: This study examined the effects of the CYP3A/P-glycoprotein inducer, rifampicin, on the pharmacokinetics of dabigatran following oral administration of the prodrug, dabigatran etexilate. METHODS: This was an open-label, fixed-sequence, four-period study in healthy volunteers. Subjects received a single dose of dabigatran etexilate 150 mg on day 1, rifampicin 600 mg once daily on days 2-8, and single doses of dabigatran etexilate on days 9, 16 and 23. RESULTS: Twenty-four subjects were treated, of whom 22 received all treatments. Relative to the reference (single dose of dabigatran etexilate alone; treatment A), administration of dabigatran etexilate following 7 days of rifampicin (treatment B) decreased the geometric mean (gMean) area under the concentration-time curve (AUC(0-infinity)) and maximal plasma concentration (C(max)) of total dabigatran by 67 and 65.5%, respectively. The time to peak and the terminal half-life were not affected. The gMean ratio for the primary comparison (treatment B vs. treatment A) was 33.0% (90% confidence interval 26.5, 41.2%) for AUC(0-infinity) and 34.5% (90% confidence interval 26.9, 44.1%) for C(max), indicating a significant effect on total dabigatran exposure (total pharmacologically active dabigatran represents the sum of nonconjugated dabigatran and dabigatran glucuronide). After a 7 day (treatment C) or 14 day washout (treatment D), the AUC(0-infinity) and C(max) of dabigatran were reduced by 18 and 20%, and by 15 and 20%, respectively, compared with treatment A, which was considered not clinically relevant. The overall safety profile of all treatments was good. CONCLUSIONS: Administration of rifampicin for 7 days resulted in a significant reduction in the bioavailability of dabigatran, which returned almost to baseline after 7 days washout.

DrugBank Data that Cites this Article

Drug Transporters

Drug	Transporter	Kind	Organism	Pharmacological Action	Actions
Dabigatran etexilate	P-glycoprotein 1	Protein	Humans	Unknown	Substrate	Details

Drug Interactions

• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental
• All Drugs

Drugs	Interaction
Integrate drug-drug interactions in your software
Dabigatran etexilate Levothyroxine	The serum concentration of Dabigatran etexilate can be decreased when it is combined with Levothyroxine.
Dabigatran etexilate Trazodone	The serum concentration of Dabigatran etexilate can be decreased when it is combined with Trazodone.
Dabigatran etexilate Mifepristone	The serum concentration of Dabigatran etexilate can be decreased when it is combined with Mifepristone.
Dabigatran etexilate Rifampicin	The serum concentration of Dabigatran etexilate can be decreased when it is combined with Rifampicin.
Dabigatran etexilate St. John's Wort	The serum concentration of Dabigatran etexilate can be decreased when it is combined with St. John's Wort.