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Substantial amounts of mezlocillin are rapidly distributed in a wide range of tissues. After intravenous administration of doses ranging form 2 to 5 g, concentrations therapeutically active against most sensitive organisms were obtained in bone, prostate, skin, muscle and liver, as well as in wound exudates, pleural exudates, sputum and bronchial secretions. Mezlocillin did not easily cross the blood-brain barrier with normal meninges, but CSF concentrations when the meninges were inflamed. The antibiotic also crossed the placenta.

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.

Drug level at receptor site dictates the intensity of the pharmacological response. The level which is achieved depends upon several factors such as gastrointestinal absorption, protein binding, distribution, biotransformations and excretion. Modification of anyone of these processes can influence drug level at the site of action and thus the therapeutic effect of the drug. Physiological and pathological states or drug interactions can influence pharmacokinetics of benzodiazepines and thus modification of dosage regimen may be necessary. The influence of aging, liver disease, drug interactions such as alcohol, antidepressants... is of importance. Consequences of these modifications are discussed.

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.