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Beraprost sodium‐fluindione combination in healthy subjects: pharmacokinetic and pharmacodynamic aspects
Author(s) -
Warot Dominique,
Berlin Ivan,
Aymard Guy,
Ankri Annick,
Fabry Caroline,
Besse Bruno,
Lechat Philippe,
Diquet Bertrand
Publication year - 2000
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.2000.tb00021.x
Subject(s) - medicine , pharmacodynamics , pharmacokinetics , placebo , cmax , crossover study , pharmacology , warfarin , vitamin k antagonist , prothrombin time , anesthesia , alternative medicine , pathology , atrial fibrillation
— Beraprost sodium (BPS), an orally active PGI2 (prostaglandine I2) analogue possesses vasodilatating and platelet aggregation inhibiting properties. It is being developed in peripheral arterial occlusive disease. As in future clinical practice BPS might be co‐prescribed with oral anticoagulants, we investigated its interaction with fluindione, a vitamin K antagonist in healthy subjects in a randomised, double‐blind, placebo‐controlled, crossover study. Twelve healthy Caucasian male subjects randomly received BPS 40 μg t.i.d. or placebo for 3 days. There was a 7 day wash out between the two treatment periods. On day 3 of each treatment, the subjects ingested concomitantly a single oral dose of 20 mg of fluindione. The main assessment criterion was fluindione's pharmacokinetics. Secondarily, pharmacodynamic measurements of coagulation (prothrombin time, and International Normalised Ratio, INR) and platelet function (in vitro closure time assessed by PFA‐100×) were performed. Fluindione was assayed by HPLC with UV detection up to 96 h post‐drug. No statistical difference could be evidenced on any fluindione pharmacokinetic parameters between BPS and placebo phases: t 1/2 (h): 35.9 (8.2) vs. 34.0 (4.2) [90% CI 105.8 (95.5–116.2)]; T max (h): 2.0 (0.5–6.0) vs. 4.0 (0.5–6.0) [90% CI 136.4 (70.7–208.9)]; C max (mg/L): 3.1 (0.6) vs. 2.9 (0.5) [90% CI 94.1 (85.8–103.2)]; AUC 0‐inf (mg/h/L): 117.0 (31.5) vs. 113.9 (33.8) [90% CI 97.6 (87.5–108.8)]. The studied doses of BPS did not affect platelet function, at least as assessed by the in vitro platelet function testing. Twenty milligrams of fluindione marginally modified the PT ratio and INR, however, no statistically significant difference was found between BPS and placebo phases. In conclusion, a 3 day regimen of BPS 40 μg t.i.d. by oral route does not seem to affect pharmacokinetic parameters of a fluindione 20 mg single dose.