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Research into individual predisposition to develop acute rhabdomyolysis attributed to fenoverine

Centre anti-poisons- Pharmacovigilance, hôpital Salvator, 249 bd. Sainte Marguerite, 13 009 Marseille

Geneviève Kozak-Ribbens

Centre de Résonance Magnétique Biologique et Médicale, Faculté de médecine, 27 bd. Jean Moulin, 13005 Marseille, France

Luc de Haro

Centre anti-poisons- Pharmacovigilance, hôpital Salvator, 249 bd. Sainte Marguerite, 13 009 Marseille

Patrick J Cozzone

Centre de Résonance Magnétique Biologique et Médicale, Faculté de médecine, 27 bd. Jean Moulin, 13005 Marseille, France

A xenobiotic, well tolerated by the majority of treated patients, can cause serious complications in patients with individual susceptibility. Based on the hypothesis that such a phenomenon may occur in rare cases of rhabdo myolysis attributed to fenoverine (DCI), we designed a protocol to look for a genetic predisposition. Six patients were included who had previously had an episode of rhabdomyolysis after taking fenoverine. A seventh patient was added, who had only experienced myalgia without cytolysis. All patients were investigated by the following tests: 31-phosphorus nuclear magnetic resonance spectro scopy, histopathological examination of the muscle, muscle contraction tests and biochemical analysis of the muscle.

All patients examined proved to have muscle abnorm alities. The pathology found varied greatly from patient to patient: mitochondrial myopathy, lipid storage myopathy, sensitivity to malignant hyperthermia or disorders of oxidative metabolism.

The probability of finding by chance such rare muscle disorders associated with the equally rare rhabdomyo lysis attributed to fenoverine is practially zero. We conclude that there is a cause and effect link between underlying abnormalities and the muscular cytolysis attributed to fenoverine.

Key Words: fenoverine • rhabdomyolysis • malignant hyperthermia • muscle oxidative dysfunction • genetic predisposition

Human & Experimental Toxicology, Vol. 15, No. 10, 815-820 (1996)
DOI: 10.1177/096032719601501004


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