Assessment of hepatic insufficiency model in the rabbit using carbon tetrachloride intoxication.

The objective of the present study was to compare two doses (0.035 and 0.1 mL/kg) of carbon tetrachloride given intragastrically or intraperitoneally to rabbits during 8 weeks to induce a model of liver insufficiency.

Microdialysis: an alternative for in vitro and in vivo protein binding studies.

The aim of the present study was to compare the performance of conventional equilibrium dialysis method with a microdialysis method in studying drug protein binding. The two methods were assessed by comparing the measured mean unbound drug fraction in different plasma species in vitro in plasma of four different species and at two concentrations of the non-indolic melatonin analog S 20098. For the microdialysis study, the unbound drug fraction was calculated after correction for membrane recovery.

Comparison of the "zero crossing" method in derivative spectroscopy and ultrafiltration for the determination of free and bound fractions of mitoxantrone.

In vitro mitoxantrone binding to human serum, human serum albumin (HSA, 600 microM) and alpha-1-acid glycoprotein (AAG, 15 microM) was investigated by ultrafiltration and the first-derivative spectrophotometry based on the "zero crossing" method. The binding of mitoxantrone to isolated proteins was studied at eight concentrations whose range depended on the protein used. The results showed that mitoxantrone binding to human plasma and HSA involved a saturable binding.

Pharmacokinetic and pharmacodynamic study of amodiaquine and its two metabolites after a single oral dose in human volunteers.

The pharmacokinetics of amodiaquine (AQ, Flavoquine, CAS 6398-98-7) and its metabolites, mono (AQml) and bis-desethyl amodiaquine (AQm2) were investigated in 8 healthy volunteers after an oral dose of 306.2 mg of AQ. Metabolic clearance was the main AQ elimination pathway.

Pharmacokinetics of 14C-N-N'-dicyclopropyl-methyl-piperazine-dichlorhydrate. 3rd communication: whole-body autoradiographic study in Cynomolgus monkeys after oral administration.

A distribution study was carried out on Cynomolgus monkeys (Macaca fascicularis) dosed orally with 14C-labelled N-N'-dicyclopropyl-methyl-piperazine-dichlor-hydrate 14C-Ino 2628-CZ and sacrificed 2, 8 and 24 h after dosage, using whole-body autoradiography. It is demonstrated that radioactivity is found in all the body; high intakes occur in melanin containing tissues, in blood-forming organs, and in accessory genital glands. Moreover, radioactivity crosses the blood-brain barrier and is mainly localized in hippocampus, caudate, putamen and frontal cortex.