Effect of lysine clonixinate on the pharmacokinetics and anticoagulant activity of phenprocoumon.
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.
Russmann
S
S
Department of Clinical Pharmacology, Herz-Zentrum Bad Krozingen, Bad Krozingen, Germany.
Dilger
K
K
Trenk
D
D
Nagyivanyi
P
P
Jähnchen
E
E
D000328:Adult; D000925:Anticoagulants / Q000493:pharmacokinetics* / Q000494:pharmacology*; D019540:Area Under Curve; D003002:Clonixin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D018592:Cross-Over Studies; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004311:Double-Blind Method; D006207:Half-Life; D006801:Humans; D008239:Lysine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008297:Male; D010644:Phenprocoumon / Q000493:pharmacokinetics* / Q000494:pharmacology*; D011517:Prothrombin Time
D000925:Anticoagulants; D016861:Cyclooxygenase Inhibitors; C089163:lysine clonixinate; D008239:Lysine; D010644:Phenprocoumon; D003002:Clonixin