No abstract

SUMMARY Trimethoprim was excreted within one hour after being given orally to the turtle Pseudemis scripta elegans. No 0-demethylated or N-oxide metabolites were detected.

1. Ferrocenylisopropylamine (FIPA) inhibits the elimination of ampheta mines in rat. The half-life of isopropylamphetamine was increased from approx. 30 to 85-100 min after administration of FIPA.2. With isolated, perfused, rat liver, the half-lives of isopropylamphetamine, biamphetamine and benzylamphetamine were increased from 5-20 min to about 200 min by equimolar amounts of FIPA, indicating that the. prolonging effect of FIPA is due to iriterference at the metabolic level.3. Experiments with hepatic microsomal suspensions demonstrated that FIPA competitively inhibits the oxidativé N-dealkylation of isopropylampheta mine ; the Ki of FIPA is 4-1 x 10_* M.4. Binding of isopropylamphetamine and FIPA to cytochrome P-450 was studied using hepatic microsomes of phenobarbital-treated rats. Isopropylamphétamine caused a type I, and FIPA a type II difference spectrum ; FIPA showed a much higher binding affinity (/Cs= 1-24 x 10 8 m) than isopropyl amphetamine (i£g = 0-96 x 10~3 m ). FIPA acts as a modifiér of the spectral changes indüced by isopropylamphetamine.5. Results suggest that the competitive inhibition of the N -dealkylation of Ar-aikylamphetamines, and thus the prolonging of their action, by FIPA is related to competition for binding to cytochrome P-450.

Sulfamonomethoxine is not O-demethylated in the snail Cepaea hortensis, but acetylated (15.2%) and oxidised (0.78%) at the 2 position of the pyrimidine nucleus.

N-pentyl-sparsomycin (PSm) is a lipophilic analogue of sparsomycin (Sm), which is a well known inhibitor of protein synthesis. This compound was selected for preclinical pharmacokinetic studies because of its high in vitro and in vivo antitumor activity. In this study in which the drug was evaluated in beagle dogs under anaesthesia, the drug concentrations in plasma, urine and bile samples were determined using high performance liquid chromatography (HPLC). Plasma protein binding was approximately 54%. The mean t1/2 beta was 0.2 hours (12 minutes) and t1/2 tau was 0.75 +/- 0.1 hours (45 +/- 6 minutes). During continuous infusions up to 5.25 hours, the steady state was reached in 3 out of 6 experiments, suggesting that in some cases the real t1/2 tau was longer than measured. PSm was actively reabsorbed from the renal tubuli. This process was saturable at the higher doses. Tubular reabsorption played only a minor role in pharmacokinetics as most of the drug (67%) was eliminated by the non-renal clearance. The non-renal clearance was saturable at higher doses of PSm and was the reason for non-linearity of pharmacokinetics.