Pharmacokinetics and dynamics of propacetamol in healthy volunteers

Eight male healthy volunteers received an intramuscular (i.m.) propacetamol 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 were collected for determining paracetamol concentrations at similar time points. Propacetamol administration produced significant analgesia with onset of action within half an hour of administration (mean +/- SD, 38.73 +/- 14.5%; p < 0.001) as compared to predose values. Peak effect was noted at 1 h (mean +/- SD 45.5 +/- 19.1%; p < 0.001). Significant analgesia was noted till the end of 2nd hour (p < 0.01). Absorption of paracetamol from i.m. site was very fast. Within half an hour, peak paracetamol concentrations (Cmax, 27.07 +/- 8.74 mu g/ml) were achieved and maintained up to 2 h (tmax, 0.93 +/- 0.49 h). This was followed by gradual decline in the concentration of paracetamol. There was good correlation with the analgesic effect and salivary paracetamol concentrations (r = 0.62).