Pentamidine: Clinical pharmacologic correlations in man and mice
Waalkes, T.P.; Denham, C.; DeVita, V.T.
Clinical Pharmacology and Therapeutics 11(4): 505-512
Patients with malignant disease complicated by diffuse interstitial pneumonia due to proved or suspected Pneumocystis carinii were given pentamidine in the dosage schedule recommended for this infection. By means of a sensitive method of assay, the plasma levels and urinary excretion of pentamidine during therapy were studied in these patients. Following the intramuscular administration of pentamidine, plasma levels were low and urinary excretion prolonged. After a single intraperitoneal injection in mice, the tissue distribution levels and excretion pattern for pentamidine were determined at various time intervals. There was storage of the drug in tissues and excretion was delayed. The highest concentration of pentamidine was found in the kidney. In mice pentamidine is eliminated primarily intact with little, if any, altered. The available data in man also suggested that pentamidine is retained, bound to tissues, and excreted over an extended period. Although renal abnormalities followed pentamidine, it was not possible to implicate the drug in all cases because of the seriousness of the illness and the concomitant use of other drugs. Pentamidine is useful in preventing disease due to Trypanosoma gambiense as well as effective in the treatment of diffuse interstitial pneumonia due to Pneumocystis carinii. The frequency of this type of pneumonia in cancer patients and in patients undergoing organ transplantation suggests the need for studies in animals and man.