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 (Vdarea 5·91/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 (t½ 2h) largely as the result of glucuronidation and sulphation of the phenolic function in the molecule. The major route of excretion is via the urine, > 70% of the dose appearing in the 0·24 h urine collection almost entirely as conjugated metabolites.4. After multiple dosing, orally or parenterally, ihere is no accumulation above that predicted from single dose kinetics.5. The pharmacok...