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E Singlas

Publications and source records attributed to E Singlas.

12 recordsLinked to original sources

Pharmacokinetics of perhexiline maleate in anginal patients with and without peripheral neuropathy.

Perhexiline maleate (Pexid) which has been in general use in France with good results for the treatment of angina pectoris since 1973, may be associated with severe side effects including peripheral neuropathy. The present study is a comparison of the pharmacokinetics of perhexiline maleate in anginal patients with and without signs of peripheral neuropathy. Compared to the latter, those with neuropathy had higher plasma levels of perhexiline, slower hepatic metabolism and a longer plasma half-life. Thus, peripheral neuropathy associated with perhexiline maleate treatment appears to be a direct toxic effect due to accumulation of the drug. The accumulation might result either from a decreased volume of distribution secondary to a loss of body weight, possibly drug-induced, or to slow hepatic metabolism of perhexiline of genetic origin or due to hepatic disease, possibly drug-induced. The neuropathy is rarely an isolated event, as it is often associated with one or more adverse effects of perhexiline.

Aged

[Perhexilline maleate: relationship between side-effects, plasma concentrations and rate of metabolism (author's transl)].

In three individuals (2 male and 1 female) with severe side-effects apparently related to the regular ingestion for a period of at least 5 months of perhexiline maleate, the authors studied the rate of fall in plasma levels of the drug, of its monohydroxylated metabolite, blood transaminase and glucose levels following the interruption of therapy. The relationship between these data would indicate two hypotheses which could be tested during future studies: the manner in which the body metabolises the drug would appear to vary in relation to plasma concentration and/or hepatic involvement.

Adult

[Neurological disorders and perhexiline maleate therapy. Clinical study of 10 cases. Neuropathological, pharmacocinetic and biochemical studies (author's transl)].

Ten new cases of perhexiline induced peripheral neuropathies are reported. The authors emphasize the possible association of other neurological disorders: cerebellar symptoms in one case, complex tremor in two other cases, marked decrease of photomotor reflexes in one case and disgeusia in another one. The pharmacocinetic study of 4 cases revealed the presence of a low metabolism of the drug in one of them. Polymorphous inclusions have been seen in Schwann cell and endothelial cell cytoplasm in the three patients with electron microscopic study of the nerves. The pathological study of one case showed the demyelination of spinal cord posterior columns. In another case, who died from hepatic coma, the biochemical study of cerebral lipids revealed the low values of cerebrosides and sulfatides in cerebellum and cerebral white matter.

Cerebellar Diseases