RELATIVE BIOAVAILABILITY OF PARACETAMOL A S SUPPOSITORIES COMPARED TOTABLETS

The relative bioavailability of paracetamol (CAS 103-90-2) in ben-u-ro n(R) 500 mg and ben-u-ron(R) 1000 mg suppositories (test formulations) was compared with that of Benuron(R) tablets 500 mg (reference produc t) in an open, individual, 3-period-changeover-study in 18 healthy sub jects. Plasma concentrations of paracetamol were determined using a sp ecific and sensitive HPLC method with UV detection. For the assessment of bioavailability AUC, C-max, t(max) and HVD were used as pharmacoki netic characteristics. Bioequivalence of the rectal formulations was t ested by calculating 90% confidence intervals using the Two-one-sided- t-tests-procedure and log-transformed data of AUC and C-max. For AUC t he confidence intervals were required to be in the 80 and 125% range, for C-max between 70 and 143% (inclusion rule). Data from 17 subjects could be evaluated. Bioavailability of paracetamol was 89 and 90% for the 500 and 1000 mg suppositories respectively compared with that of t he 500 mg reference tablets. Mean maximum paracetamol plasma concentra tions (C-max) were 3.55 and 6.02 or 7.16 mg/l after administration of the 500 and 1000 mg suppositories or the 500 mg tablets, respectively. These maximum concentrations were achieved 2.0, 2.7 and 0.6 h (t(max) ) after administration of the respective preparations. The correspondi ng HVD values were 4.3, 5.2 and 2.0 h, respectively. After dose adjust ment of the results for the 1000 mg suppositories relative bioavailabi lities of paracetamol from both rectal formulations exceeded 80% of th at from the tablets. As would be expected, the rate of absorption from the rectal formulations was somewhat slower than that of the oral for mulation (500 mg tablets). These results prove an appropriate bioavail ability of paracetamol from both suppositories when compared with the tablets. After dose correction for the 1000 mg suppositories, both rec tal preparations were assessed to be bioequivalent.