The pharmacokinetics of the new angiotensin converting enzyme (ACE) inhibitor benazepril.HCl were evaluated in healthy male volunteers. The single dose kinetics were established from data of 62 subjects receiving an oral 10 mg dose of the drug. The steady state kinetics were investigated in 15 subjects after once-daily oral doses of 5, 10 or 20 mg. The compound is a prodrug which, on absorption, is hydrolysed to the pharmacologically active metabolite benazeprilat. Thus, plasma concentrations and urinary excretion of parent compound and active metabolite were determined. Benazepril.HCl was rapidly absorbed (tmax = 0.5 h) and rapidly eliminated from plasma (t1/2 = 0.6 h). Only trace amounts were excreted unchanged in urine. The drug was rapidly metabolized to benazeprilat (tmax = 1.5 h). The elimination of the metabolite from plasma was biphasic. About 80 per cent of benazeprilat formed was eliminated within 24 h (t 1/2 = 2.7 h), whereas the terminal phase (t1/2 = 22.3 h) controlled a minor amount of elimination. About 17 per cent of dose was excreted in the 24-h urine as benazeprilat. The drug disposition did not change during repeated oral dosing and only small accumulation of the metabolite occurred. The accumulation ratio was 1.20 for AUC and 1.24 for urinary excretion. The effective half-life for accumulation was estimated at about 10-11 h. The comparison with other ACE inhibitors showed similarities but also marked differences with respect to the drug kinetics and excretion.

Adult↗

PubMedDate not supplied

Correlates of pathological gambling propensity in prison inmates.

The South Oaks Gambling Inventory was administered to 136 consecutively admitted inmates in a medium-security prison in Nevada. According to the criteria of the authors of this instrument, 22.79% of these inmates had some problem and 26% were probable pathological gamblers. Significant positive correlations with the F, depression, psychopathic deviate, psychasthenia, paranoia, schizophrenia, and Mac Andrew alcoholism scales of the Minnesota Multiphasic Personality Inventory (MMPI) were found. Gambling score was negatively correlated with the Raven's Standard Progressive Matrices measure of intelligence. Clinical implications are suggested.

Adult↗

PubMedDate not supplied

Differential mutagenic activity of IQ (2-amino-3-methylimidazo[4,5-f]quinoline) in Salmonella typhimurium strains in vitro and in vivo, in Drosophila, and in mice.

IQ, a heterocyclic aromatic amine which is formed during the frying of meat, was prepared by chemical synthesis. Its genotoxic potential was studied in bacteria, Drosophila and in mice. A mutagenic effect of IQ (frameshift induction) was detected in Salmonella typhimurium in experiments without metabolic activation; this effect was several orders of magnitude lower than that observed in the presence of an activation system. Ames tests with liver-homogenate S9 fraction from PCB-induced mice and rats confirmed the high mutagenic potency of IQ metabolites (Kasai et al., 1980a). Comparative studies on diagnostic Salmonella strains revealed that the high frameshift-inducing activity is independent of the plasmid pkM101; it is, however, greatly reduced by an intact excision-repair system for DNA lesions. The mutagenic activity of the metabolite(s) formed in vitro by S9 mix has a half-life of ca. 14 min. In the fruit fly, Drosophila melanogaster, IQ induced when used at sublethal concentrations, X-chromosomal recessive lethal mutations in male germ cells in a dose-dependent manner. In mice, tests were performed to detect somatic mutations: chromosomal anomalies (micronuclei) in bone marrow, and gene mutations (affecting coat pigmentation) in mice exposed to IQ in utero. No genotoxic effects were observed in these assays. However, the formation of mutagenic metabolites in the liver of IQ-treated mice was unequivocally demonstrated in host-mediated assays using Salmonella as mutagen probes in mice. The data demonstrate genotoxic activity of IQ in prokaryotic and eukaryotic organisms. The possible reasons for the different response of mammalian systems in vivo and the Salmonella system are discussed.

Animals↗

PubMedDate not supplied

Problems of diagnosis and treatment in the Dandy-Walker syndrome.

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Child, Preschool↗

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[Sterility problem and objective determination of ovulation].

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Adult↗