PHARMACOKINETICS AND DYNAMICS OF PROPACETAMOL IN HEALTHY-VOLUNTEERS

Eight male healthy volunteers received an intramuscular (i.m.) propace tamol 1 gm, a prodrug of paracetamol. Analgesic activity was evaluated against pressure-induced pain (sphygmomanometer) at 0, 0.5, 1, 2, 3, 4, 5 and 6 hours after the drug administration. The salivary samples w ere collected for determining paracetamol concentrations at similar ti me points. Propacetamol administration produced significant analgesia with onset of action within half an hour of administration (mean +/- S D, 38.73 +/- 14.5%; p < 0.001) as compared to predose values. Peak eff ect was noted at 1 h (mean +/- SD 45.5 +/- 19.1%; p < 0.001). Signific ant analgesia was noted till the end of 2nd hour (p < 0.01). Absorptio n of paracetamol from i.m. site was very fast. Within half an hour, pe ak paracetamol concentrations (Cmax, 27.07 +/- 8.74 mu g/ml) were achi eved and maintained up to 2 h (tmax, 0.93 +/- 0.49 h). This was follow ed by gradual decline in the concentration of paracetamol. There was g ood correlation with the analgesic effect and salivary paracetamol con centrations (r = 0.62).