A placebo‐controlled pharmacodynamic and pharmacokinetic interaction study between tamsulosin and acenocoumarol

Abstract

Aim To evaluate pharmacokinetic and pharmacodynamic interactions between tamsulosin and acenocoumarol. Methods Twelve healthy volunteers received tamsulosin 0.4 mg or placebo once daily for 9 days in a double-blind, cross-over study. On day 5 of each study period, a single 10-mg oral dose of racemic acenocoumarol was administered. Results The ratios (point estimates (90% confidence intervals)) of values in the presence and absence of tamsulosin were: AUC PT 1.01 (0.98, 1.03); maximum prothrombin time (Pt max ) 0.99 (0.94, 1.05); AUC (R)-acenocoumarol 1.02 (0.90, 1.16), and AUC (S)-acenocoumarol 1.03 (0.89, 1.20). Both combinations, tamsulosin and placebo with acenocoumarol, were well-tolerated. Conclusions Multiple doses of tamsulosin had no effect on the pharmacokinetics or pharmacodynamics of a single high dose of acenocoumarol.

Acenocoumarol’s pharmacokinetic: linear or not?

“…Various studies have reported the AUC 0-48 and AUC 0-∞ values of acenocoumarol for 1, 4, 10 and 12 mg dose (Table 1(Tab. 1); References in Table 1: Huang et al, 2008[2]; Masche et al, 1999[3]; Popovic et al, 1994[4]; Rolan et al, 2003[6]; Sasso et al, 2012[8]; Sunkara et al, 2004[9]; Thijssen and Baars, 1983[10]; Thijssen and Hamulyàk, 1989[12]). No other information on AUC 0-48 and AUC 0-∞ were available with the 2, 8 and 16 mg dose.…”

Bioequivalence of Acenocoumarol in Chilean Volunteers: an Open, Randomized, Double-Blind, Single-Dose, 2-Period, and 2-Sequence Crossover Study for 2 Oral Formulations

“…Other limitation of this study could be the use of a single dose from 4 mg tablet of acenocoumarol, considering that AUC values of plasma concentrations versus time are proportional to the administered dose in a higher range [8-16mg]. Finally, similar to other oral anticoagulants, acenocoumarol exhibits a narrow therapeutic index [ 30 ] , therefore we recommend that any patient who switches between reference product and generic formulation should be carefully monitored according to the International Normalized Ratio (INR) [ 31 ] .…”