RELATIVE BIOAVAILABILITY STUDIES ON PARAC ETAMOL IN SUPPOSITORIES AS COMPARED TO TABLETS

Relative bioavailabilities of 250 mg paracetamol (GAS 103-90-2) in ben -u-ron(R) 125 mg and ben-u-ron(R) 250 mg suppositories were determined in comparison with that of cut-in-half Benuron(R) tablets 500 mg in a n open intraindividual 3-period-changeover-study in 18 healthy volunte ers. Plasma concentrations of paracetamol were analyzed by means of a specific and sensitive HPLC-method with UV-detection. For the assessme nt of the bioavailability AUC, C-max, t(max), and HVD (half value dura tion) were used as pharmacokinetic characteristics. Relative bioavaila bility of paracetamol was 102% for 125 mg and 93% for 250 mg supposito ries, compared with that of cut-in-half 500 mg tablets. Mean maximum p aracetamol plasma concentrations (C-max) were determined as 2.1 mu g/m l (CV = 31%; (CV = Coefficient of Variation), 2.0 mu g/ml (CV = 27%) a nd 3.5 mu g/ml (CV = 27%) after administration of 125 mg and 250 mg su ppositories and 500 mg cut-in-half tablets, respectively. These maximu m concentrations were achieved 2.2 +/- 0.7, 1.8 +/- 0.7 and 0.6 +/- 0. 3 h (t(max)) after administration of the respective preparations. The corresponding HVD-values were 3.8 +/- 1.0, 3.5 +/- 0.9 and 1.8 +/- 0.8 h, respectively. Extent of bioavailability of paracetamol (dose: 250 mg) following administration of 125 mg as well as 250 mg suppositories in comparison with 500 mg tablets was shown to be equivalent. The res ults obtained in this study confirm the adequate bioavailability of bo th suppositories compared with tablets. On the other hand both supposi tory preparations were assessed as being bioequivalent concerning AUC and C-max.