Use of a specific and sensitive assay to determine pentamidine pharmacokinetics in patients with AIDS.
The first-dose pharmacokinetics of pentamidine were studied in patients with AIDS. Pentamidine isethionate (4 mg/kg) was administered intramuscularly or intravenously to two groups of six patients each. Serial plasma and urine concentrations were measured by high-performance liquid chromatography, which is accurate and precise (sensitivity limits, 2.29 ng/ml in plasma and 229 ng/ml in urine). The mean peak concentrations in plasma after intramuscular and intravenous administration were 209 ng/ml and 612 ng/ml, respectively. Plasma concentrations, which declined biexponentially, were detectable throughout the 24-hr dosing interval and fell to less than 25 ng/ml after 8 hr. The mean plasma clearance, elimination half-life, apparent volume of distribution, and apparent volume at steady state for intramuscularly treated patients were 305 liters/hr, 9.36 hr, 924 liters, and 2,724 liters, respectively; these parameters for intravenously treated patients were 248 liters/hr, 6.40 hr, 140 liters, and 821 liters, respectively. Renal clearance of pentamidine was 5.0% of the plasma clearance for intramuscularly treated patients and 2.5% for intravenously treated patients. We found significant differences in the pharmacokinetic parameters between intramuscularly and intravenously treated patients.
D000163:Acquired Immunodeficiency Syndrome / Q000378:metabolism*; D000328:Adult; D000578:Amidines / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003404:Creatinine / Q000097:blood; D006716:Homosexuality; D006801:Humans; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D010419:Pentamidine / Q000097:blood / Q000378:metabolism* / Q000652:urine; D011020:Pneumonia, Pneumocystis / Q000378:metabolism
D000578:Amidines; D010419:Pentamidine; D003404:Creatinine