Pharmacologic aspects of pentamidine
Waalkes, T.P.; Makulu, D.R.
National Cancer Institute Monograph 43: 171-177
Pentamidine is an aromatic diamidino compound synthesized originally for the therapy of trypanosomiasis. The pharmacologic effects of pentamidine vary, depending on its route of administration. In animals, the dominant effects have been a precipitous, transitory drop in blood pressure after injection and renal toxicity following repeated administration. To avoid the possibility of immediate toxic reactions associated with iv administration, we now usually give the drug im to humans. Further interest in pentamidine has been stimulated by its usefulness in the treatment of interstitial pneumonia caused by Pneumocystis carinii. In some patients receiving antineoplastic or immunosuppressive therapy who have superimposed P. carinii pneumonia, pentamidine may cause serious renal toxicity. Distribution and excretion studies in animals indicate pentamidine is deposited in tissues, with the greatest concentration in the kidneys, and gradually eliminated over a prolonged period. The mechanism of action of pentamidine against P. carinii or the means whereby fixation in tissues and subsequent toxicity occur have not been elucidated. Recent investigations to help clarify these points indicate that pentamidine inhibits dihydrofolate reductase in all tissues studied both in vitro and in vivo. In addition, pentamidine interacts and forms water-insoluble products with specific nucleotides and nucleic acids.