W F Hoffman — Page 3 | PubMed Health

PubMedDate not supplied

Acute extrapyramidal syndromes in neuroleptic-treated elders: a pilot study.

The incidence, morbidity, and risk factors for acute extrapyramidal syndromes (EPS) such as akathisia and drug-induced parkinsonism (DIP) in neuroleptic-treated elders have not been systematically explored. This study presents data on 17 elderly patients who were prospectively examined for up to 4 weeks for acute EPS, functional and cognitive status, and behavioral disturbances. Seventy-one percent of subjects developed DIP, and 18% developed akathisia. Predictors of DIP included pre-neuroleptic treatment parkinsonian signs and neuroleptic dose, despite use of low doses of neuroleptics. Development of acute EPS was associated with failure to improve behaviorally. New-onset urinary incontinence was the most common functional abnormality.

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PubMedDate not supplied

Biotransformation of lovastatin. I. Structure elucidation of in vitro and in vivo metabolites in the rat and mouse.

Structures of in vitro microsomal and in vivo metabolites of lovastatin, a new cholesterol-lowering drug, were elucidated with the combined application of HPLC, UV, fast atom bombardment-MS, and NMR spectroscopy. Liver microsomes from rats and mice catalyzed the biotransformation of lovastatin, primarily at the 6'-position of the molecule, to form 6'-hydroxy-lovastatin and a novel 6'-exomethylene derivative. Hydroxylation at the 6'-position occurred stereoselectively, giving 6'-beta-hydroxy-lovastatin. Stereoselective hydroxylation at the 3"-position of the methylbutyryl side chain and hydrolysis of the lactone group to the corresponding hydroxy acid were the other two pathways of microsomal metabolism. 3'-Hydroxy-iso-delta 4',5'-lovastatin was isolated, but is not believed to be a direct metabolite since 6'-beta-hydroxy-lovastatin rearranges to this compound under mildly acidic conditions. The major metabolites excreted in bile of rats treated with the hydroxy acid form of the drug were identified as the 3'-hydroxy analog and a taurine conjugate of a beta-oxidation product of lovastatin. The pentanoic acid derivative of lovastatin, formed by beta-oxidation of the heptanoic acid moiety, was a major metabolite in livers of mice dosed with the hydroxy acid form of lovastatin. The microsomal metabolites, in their hydroxy acid forms, were active inhibitors of HMG-CoA reductase. The relative enzyme inhibitory activities of hydroxy acid forms of lovastatin, 6'-beta-hydroxy-, 6'-exomethylene-, and 3"-hydroxy-lovastatin were 1, 0.6, 0.5, and 0.15, respectively.

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