Abstract
We developed a sensitive and specific agar-diffusion bioassay for pentamidine by using an amphotericin B-resistant isolate, Candida tropicalis ATCC 28707, as the test organism. We determined levels of pentamidine in serum of rats given intramuscular or intravenous injections and levels in serum, urine, and tissues of humans who had received the drug by slow intravenous infusion. Rats given intravenous pentamidine at a dose of 2 mg/kg had higher serum levels than those given intramuscular injection at a dose of 10 mg/kg; however, the drug was detectable in serum for 4 hr after intramuscular administration. The serum half-life in rats after intravenous injection was 2 min. Humans treated with 4 mg of pentamidine/kg by slow (1-2 hr) intravenous infusion had peak serum concentrations ranging from 0.5 to 3.4 micrograms/ml. The mean half-life of elimination from serum in humans was 17 +/- 4 min (n = 3). In two patients, studied after completion of therapy, urinary excretion rates declined with a half-life of five and nine days. In tissues obtained at autopsy from four patients who had received pentamidine, the drug was present in highest concentration in the spleen and liver, followed by kidneys, adrenals, and lungs.
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