The clinical pharmacokinetics and metabolism of the analgesic meptazinol.
1. The analgesic drug meptazinol is rapidly and completely absorbed after oral, intramuscular (i.m.) and rectal dosage. However, the absolute bioavailability of the drug following oral dosage is low (4.5-8.7%). Rectal administration leads to a higher bioavailability (15.5%) while after i.m. dosage the drug is totally systemically available. 2. Meptazinol is widely distributed outside the vasculature (Vd*area 5.9 l/kg) partly due to the low degree of binding to plasma proteins (27% bound) and also the relatively high lipophilicity of the unionized species (log P = 2.7). 3. Elimination of the drug from plasma proceeds rapidly (t1/2 2 h) largely as the result of glucuronidation and sulphation of the phenolic function in the molecule. The major route of excretion is via the urine, greater than 70% of the dose appearing in the 0-24 h urine collection almost entirely as conjugated metabolites. 4. After multiple dosing, orally or parenterally, there is no accumulation above that predicted from single dose kinetics. 5. The pharmacokinetics of the drug are generally unaltered by age (neonates to geriatrics) and pregnancy. Renal disease also has no effect in this respect, although cirrhotic liver disease results in up to a 4-fold increase in oral bioavailability. 6. Only limited data are available on the pharmacokinetics of meptazinol when given with other drugs. Alcohol appears to have no effect, while general anaesthesia appears to reduce clearance of the drug.
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Drug Metabolism and Pharmacokinetics Section, Wyeth Research Ltd., Maidenhead, Berkshire, UK.
D000328:Adult; D000368:Aged; D001381:Azepines / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007674:Kidney Diseases / Q000378:metabolism; D008103:Liver Cirrhosis / Q000378:metabolism; D008107:Liver Diseases / Q000378:metabolism; D008297:Male; D008621:Meptazinol / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D011247:Pregnancy; D014018:Tissue Distribution
D001381:Azepines; D008621:Meptazinol