Changes in disposition kinetics of sulphadimidine in response to acute regional liver damage in sheep

Disposition kinetics of sulphadimidine in sheep, before and after regional liver damage by allyl alcohol, was investigated following a single IV injection (100 mg/kg). Allyl alcohol (12 mg/kg) provoked periportal liver lesion in 60 per cent of the animals. In normal sheep the mean elimination half-life of sulphadimidine was 7.47 +/- 1.09 hours. Liver damage significantly increased this value to 11.68 +/- 1.09 hours. Liver damage by allyl alcohol significantly changed the total body clearance (C1B), the overall elimination rate constant (beta) and the micro-constants k12 and kCl. The apparent volume of distribution (Vd) and the micro-constant k21 were not influenced by liver damage. The mean minimum steady-state concentration (Cp[min]) in normal sheep (38.43 micrograms/ml at 24 hours of interval) was found to be higher than previously reported. Liver intoxication significantly increased this value to 94.38 micrograms/ml. It is suggested that the regional liver damage has affected both the elimination and biotransformation of sulphadimidine.