No abstract

We used a bioassay to measure pentamidine concentrations in autopsy specimens from 22 patients with AIDS. Patients received pentamidine isethionate (approximately 4 mg/kg per day) parenterally for Pneumocystis carinii pneumonia; one received monthly prophylaxis. We found that lung levels of 30 micrograms/g were achieved only after the fifth dose; tissue accumulation was usually greater in the liver, kidney, adrenal, and spleen than in the lung; detectable levels were present in some tissues as late as one year after the last dose; and low but detectable levels were present in the brain of six of 17 patients. Two patients had no detectable lung levels after two days of therapy; one had a level of 17.5 micrograms/g after four doses, and two had levels of 30 micrograms/g after five doses. A more rapid and effective method of delivery, such as aerosol, should achieve higher concentrations earlier. Because pentamidine persists in lung tissue over days to weeks, daily administration may not be necessary.

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.