The relative bioavailability of paracetamol and codeine after oral administration of a combination of buclizine, paracetamol and codeine, with or without docusate, and of paracetamol alone in healthy volunteers.

A randomized, double-blind, crossover study was carried out in 10 healthy volunteers to investigate whether the inclusion of the wetting agent docusate sodium (10 mg) in a combined oral formulation ('Migraleve') with buclizine hydrochloride (6.25 mg), codeine phosphate (8 mg) and paracetamol (500 mg) had any effect on the bioavailability of the analgesics. On 3 occasions at weekly intervals, the subjects were given 2 tablets of the standard formulation, the combination without docusate or 500 mg paracetamol alone. Blood samples were taken before and at fixed times during the 4 hours after administration of each preparation for estimation of plasma concentrations of paracetamol, by gas-liquid chromatography, and of codeine, by radioimmunoassay. The results showed that there were no significant differences between the mean paracetamol concentrations achieved after administration of each of the 3 preparations at any of the time points. Peak paracetamol plasma concentrations were 11.25 +/- 1.74 micrograms/ml at 0.5 hours, 9.6 +/- 1.04 micrograms/ml at 0.75 hours, and 9.53 +/- 1.66 micrograms/ml at 0.5 hours, respectively, after the standard formulation, the combination without docusate, and paracetamol alone. Mean elimination half-lives for paracetamol were 2.83 +/- 0.51, 1.92 +/- 0.20 and 2.49 +/- 0.46 hours, respectively, and the differences were not significant. The difference between mean plasma concentrations of codeine after the two preparations including this analgesic bordered on significance at 3 hours and was significant at 4 hours, but the areas under the curve were not significantly different. Peak codeine plasma concentrations after the standard formulation were 42.1 +/- 9.4 ng/ml at 0.75 hours compared with 36.9 +/- 3.4 ng/ml at 1.5 hours after the combination without docusate.(ABSTRACT TRUNCATED AT 250 WORDS)

RCT Entities:   Population Interventions Outcomes