The kinetics of amiloride was investigated in plasma, urine, faeces and tissues of rats after oral (10 mg/kg) and i.v. (10 mg/kg bolus and 35 microg/h for 4-days infusion) administration. Initially the experimental data were analyzed by a multiexponential model, then a compartmental model was developed to describe the drug kinetics in plasma, urine, faeces and tissues after the i.v. bolus and the oral administration simultaneously. Aim of the model was also to predict the drug kinetics in plasma and tissues of rats after continuous i.v. infusion. The results of the prediction and the discrepancies between prediction and observed data allowed a deeper insight into the pharmacokinetics of amiloride.

Administration, Oral↗

PubMedDate not supplied

Inhibition of ornithine-decarboxylase produced by S(+) and R(-) ibuprofen in rats.

The differences between the S(+) and R(-) ibuprofen enantiomers in anti-inflammatory activity were assayed by measuring the release of 14CO2 in rats treated with labelled 14COOH-ornithine. Furthermore we investigated in vitro the inhibitory activity on ornithine-decarboxylase and the anti-inflammatory activity of R(-) and S(+) ibuprofen by using the carrageenin-induced paw oedema test in the rat.

Animals↗

PubMedDate not supplied

Pharmacokinetics of heptastigmine in rats.

Heptastigmine is a new long acting cholinesterase inhibitor that affects behaviour in a number of cognitive tests in animals. We have studied its pharmacokinetics in rats: plasma kinetics were evaluated after single intravenous dose (2 mg/kg), intramuscular (4 mg/kg) and oral (4 and 8 mg/kg) administration. Tissue distribution (heart, liver, kidney and brain) was studied after single intramuscular (4 mg/kg) and oral (8 mg/kg) administration. Plasma and tissue kinetics were also investigated after repeated oral doses (8 mg/kg b.i.d. for 7 days). Heptastigmine levels in plasma and tissues were determined using an HPLC method with an electrochemical detector. After a single dose, heptastigmine remained for a long time in plasma (the terminal half-life was about 12 h), distributed widely in tissues (the volume of distribution was about 61) and brain concentrations were very high (4-22 times those found in plasma). After repeated oral doses, the drug levels increased in plasma and, to a lesser extent, in liver and kidney.

Administration, Oral↗

PubMedDate not supplied