Effect of Lysine Clonixinate on the Pharmacokinetics and Anticoagulant Activity of Phenprocoumon
| Autor: | Karin Dilger, E. Jähnchen, Stefan Russmann, Dietmar Trenk, Patricia Nagyivanyi |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Adult
Male Pharmacology Phenprocoumon Double-Blind Method Pharmacokinetics Oral administration Drug Discovery medicine Humans Ingestion Cyclooxygenase Inhibitors Prothrombin time Cross-Over Studies medicine.diagnostic_test business.industry Lysine Anticoagulants Clonixin Free fraction Area Under Curve Concomitant Prothrombin Time Lysine clonixinate business Half-Life medicine.drug |
| Zdroj: | Arzneimittelforschung. 51:891-895 |
| ISSN: | 1616-7066 0004-4172 |
| Popis: | The effect of the non-steroidal anti-inflammatory drug lysine clonixinate ([2-(3-chloro-o-toluidino)nicotinic acid]-L-lysinate, CAS 55837-30-4) on the pharmacokinetics and anticoagulant activity of phenprocoumon (4-hydroxy-3-(1-phenylpropyl)-coumarin, CAS 435-97-2) was investigated in an open, randomised, two-fold, cross-over study in 12 healthy male volunteers. These subjects received a single dose of 18 mg phenprocoumon without or with concomitant treatment with lysine clonixinate (125 mg five times a day for 3 days before and 13 days after ingestion of a single dose of phenprocoumon). Pharmacokinetic parameters of phenprocoumon following oral administration were: CL/f: 0.779 +/- 0.157 ml/min, half-life of elimination: 147.2 +/- 19.9 h; free fraction in serum: 0.51 +/- 0.20%. These parameters were not significantly altered by concomitant treatment with lysine clonixinate. Prothrombin time increased from 13.3 +/- 1.3 s (at time 0) to 17.7 +/- 2.7 s following phenprocoumon and from 13.3 +/- 1.2 s to 18.0 +/- 2.2 s following combined administration. Prothrombin time returned to the pretreatment values 240 h after administration of phenprocoumon. The integrated effect (AUEC0-288 h) was identical following both treatments (4.303 +/- 461 and 4.303 +/- 312 s x h for phenprocoumon alone and phenprocoumon with lysine clonixinate, respectively). Thus, lysine clonixinate administered in therapeutic doses does not affect the pharmacokinetics and anticoagulant activity of phenproxoumon. |
| Databáze: | OpenAIRE |
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