A pharmacokinetic study of alpha 1-antitrypsin (ATT) was performed in 2 groups of homozygous PiZ-deficient patients (treated and untreated) and 1 group of healthy volunteers. The distribution of the 131I-labelled protein corresponds to a 3-compartment model. The intravenously administered protein diffused quickly to the extravascular compartment where some retention occurred. No significant difference in AAT metabolism was observed between the 3 groups. The half-life of the injected protein is slightly longer than 2.5 days. The AAT protein was not stored. These results confirm the observations collected during the clinical trials. That is, a weekly infusion is necessary to obtain stable serum AAT concentrations. Monthly infusions are unable to maintain a 'plateau' phase. The periodicity may be limited to every 2 weeks.

1. The in vivo S-oxidation of albendazole was measured from the pharmacokinetic profile of albendazole sulphoxide and sulphone determined in young male sheep receiving oral albendazole (1.9 mg/kg). Studies were carried out before, and each month after, oral infestation by 150 metacercariae of Fasciola hepatica. 2. Parasitic pathology was ascertained by clinical observation of animals, and the increase in plasma antibodies directed against liver flukes. 3. Rate of conversion of sulphoxide to sulphone and rate of sulphone elimination, were respectively decreased by 47% and 87% at week 8 post-infection, whereas significant increases in the area under plasma sulphone concentrations versus time curve and mean residence time, occurred 4-12 weeks following the infestation. 4. A 58% decrease in albendazole sulphonation was demonstrated in liver microsomal preparations obtained from 8-week-infected sheep, while there was no change in the FAD-directed sulphoxidation of albendazole. 5. The transient impairment of albendazole sulphonation could be related to the decrease in liver microsomal cytochrome P450-dependent monooxygenases observed in sheep with a similar parasitic pathology.

1. The pharmacokinetics of i.v. antipyrine (25 mg/kg) used as a model compound, were determined in young male sheep, before and each month after an oral infestation by 150 metacercariae of Fasciola hepatica, and 8 weeks following a flukicidal treatment. 2. The parasitic pathology was ascertained by the clinical observation of animals and the increase in plasma antibodies directed against liver flukes. 3. A significant decrease in the total plasma clearance of the drug occurred by week 4 to 16, and a 1.7 fold increase in mean residence time occurred by week 12 post-infection. 4. Urinary excretion of antipyrine metabolites was determined before and 8 weeks following the infestation. 4-Hydroxyantipyrine was the major urinary metabolite and its excretion was decreased by 30% in infected sheep, whereas there was no change in the excretion of norantipyrine, 3-hydroxymethylantipyrine or unmetabolized drug. 5. It is concluded that the impairment of antipyrine clearance in the course of fascioliasis could be related to the decrease in liver microsomal cytochrome P-450-dependent mono-oxygenases observed in sheep with a similar parasitic burden.