The influence of Org 10172, a low molecular weight heparinoid, on antipyrine metabolism and the effect of enzyme induction on the response to Org 10172.
1. We have investigated the effect of repeated s.c. Org 10172 (a low molecular weight heparinoid; Lomoparan) treatment (1000 anti-Xa units twice daily for 5 days) on antipyrine (500 mg orally) metabolism, and the effect of enzyme induction by pentobarbitone (100 mg for 12 days) on the pharmacokinetics and pharmacodynamics of Org 10172 following an intravenous bolus injection of 3250 anti-Xa units. 2. Org 10172 treatment caused a small increase in the formation rates of all antipyrine metabolites (P less than 0.05), while the overall kinetics of antipyrine did not change significantly. 3. Oxidative enzyme induction by pentobarbitone, as demonstrated by an increased clearance of antipyrine, was associated with an increase in the area under the anti-thrombin activity vs time curve (P less than 0.05). No influence was seen on the kinetics of plasma anti-Xa and thrombin generation inhibiting (TGI) activity. 4. The pharmacodynamics of Org 10172, as determined by clotting tests, was not influenced by enzyme induction. 5. The clinical relevance of these observations is likely to be limited.
De Boer
A
A
Center for Bio-Pharmaceutical Sciences, University of Leiden, The Netherlands.
Stiekema
J C
JC
Danhof
M
M
Breimer
D D
DD
D000284:Administration, Oral; D000328:Adult; D000983:Antipyrine / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics; D002809:Chondroitin Sulfates; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003871:Dermatan Sulfate; D004347:Drug Interactions; D004790:Enzyme Induction / Q000187:drug effects; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006025:Glycosaminoglycans / Q000494:pharmacology*; D006496:Heparinoids / Q000494:pharmacology; D006497:Heparan Sulfate; D006801:Humans; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D010424:Pentobarbital / Q000494:pharmacology
D000983:Antipyrine; D002809:Chondroitin Sulfates; D003577:Cytochrome P-450 Enzyme System; D003871:Dermatan Sulfate; D005343:Fibrinolytic Agents; D006025:Glycosaminoglycans; D006496:Heparinoids; D006497:Heparan Sulfate; D010424:Pentobarbital; C035838:danaparoid