Effect of l-propoxyphene on plasma levels and analgesic activity of d-propoxyphene in the rat.
Oral administration of l-propoxyphene with d-propoxyphene enhances the analgesic activity of d-propoxyphene as expressed in the rat tail heat test. The combination of d- and l-propoxyphene at a dose of 10 mg/kg each was found to have activity in the analgesic assay equivalent to that observed with d-propoxyphene at a dose of 20 mg/kg. In the same test, l-propoxyphene at a dose of 40 mg/kg had no activity. Co-administration of equal amounts of l-propoxyphene with d-propoxyphene (10 mg/kg p.o.) results in an increase in circulating plasma levels of d-propoxyphene from 9 +/- 2 to 114 +/- 39 ng/ml 15 minutes after administration. The increase in plasma levels is accompanied by a proportional increase in the brain and lung levels with no significant change in the liver levels. When d-propoxyphene (4 mug/ml) was infused in the isolated perfused rat liver, over 98% of the drug was extracted in a single pass through the liver. When l-propoxyphene was added to the perfusate (4 mug/ml), the extraction of d-propoxyphene was decreased to less than 90%. These results indicate that l-propoxyphene increases the systemic availability of d-propoxyphene by altering the amount of d-propoxyphene extracted by the liver.
D000284:Administration, Oral; D000700:Analgesics; D000818:Animals; D011431:Dextropropoxyphene / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D066298:In Vitro Techniques; D007279:Injections, Subcutaneous; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011930:Reaction Time / Q000187:drug effects; D013237:Stereoisomerism
D000700:Analgesics; D011431:Dextropropoxyphene