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The effects of inducing agents on the metabolism of pentamidine by isolated rat hepatocytes

Atsriku, C. and Grant, M.H. and Skellern, G.G. and Watson, D.G. (2004) The effects of inducing agents on the metabolism of pentamidine by isolated rat hepatocytes. Toxicology, 194 (3). pp. 234-235. ISSN 0300-483X

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Abstract of toxicology paper. The aromatic diamidine, pentamidine isethionate, has been used for over four decades for the chemotherapy of African human trypanosomiasis (sleeping sickness) in affected areas world-wide (Goa and Campoli-Richards, 1987). Pentamidine (P) is also used for the treatment of Pneumocyctis carinii pneumonia commonly associated with AIDS victims and over 45% of patients who receive the drug are known to suffer severe adverse reactions (Sands et al., 1985). However, emergence of drug resistant strains of trypanosomes has become a major barrier to the efficacy of trypanocidal diamidines (Peregrine, 1994). In view of poor prospects for new drug development, attempts to sustain efficacy of the drug have focussed on research into the causes of parasite drug resistance as well as drug toxicity. The inhibition or induction of hepatic drug metabolising enzymes following multiple drug therapy or exposure to environmental chemicals can alter the metabolism profile and pharmacokinetics of a given drug, leading to either a toxicological response or therapeutic failure. The aim of this study was to investigate the effects of two classical cytochrome P450 inducers, phenobarbitone (PB) and 3-methylcholanthrene (3MC), as well as a pyrethroid insecticide, deltamethrin (DM), on the metabolism of P by isolated rat hepatocytes.