Pentamidine Pharmacokinetics in Patients with AIDS with Impaired Renal Function

• Published in: The Journal of infectious diseases Vol. 156; no. 6; pp. 885 - 890
• Main Authors: Conte, John E., Upton, Robert A., Lin, Emil T.
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 01-12-1987; University of Chicago Press
• Subjects: Acquired Immunodeficiency Syndrome - complications; Acquired Immunodeficiency Syndrome - metabolism; Adult; Adults; Amidines - pharmacokinetics; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Biological and medical sciences; Blood plasma; Child; Dialysis; Dialysis solutions; Dosage; Female; Half lives; Half-Life; Humans; Infant; Infusions, Intravenous; Injections, Intramuscular; Kidney Failure, Chronic - complications; Kidney Failure, Chronic - metabolism; Male; Medical sciences; Middle Aged; Original Articles; Pentamidine - administration & dosage; Pentamidine - pharmacokinetics; Peritoneal Dialysis; Pharmacokinetics; Pharmacology. Drug treatments; Prospective Studies; Renal clearance; Renal Dialysis; Renal function; Urine; Infection; Human; Chemotherapy; Viral disease; Renal failure; AIDS; Pharmacokinetics
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/156.6.885

In patients with normal renal function, pentamidine elimination half-life and plasma clearance (mean ± SD) were 6.22 ± 1.17hr and 411 ± 55 liters/hr, respectively. With creatinine clearances from 35 to 145 ml/min, neither the elimination half-life (P = .47) nor the plasma clearance (P = .40) was correlated with renal function. Plasma concentrations in patients receiving dialysis ranged between 5.9 and 582 ng/ml and appeared not to be significantly affected by dialysis. The number of prior doses and the elimination half-life estimated from the terminal slope were correlated (r = .81, P = .025), and the results suggested that the current assay technology is still not sensitive enough to detect true elimination half-life. Trough plasma concentrations ranged between 4.3 and 67.5 ng/ml (28.4 ± 26.6 ng/rnl) in patients who had received prior doses of pentamidine, a result suggesting that drug accumulation occurs with multiple dosing. The data suggest that dosage adjustments are not necessary with creatinine clearances of <35 ml/min. Because multiple dosing leads to increased trough concentrations and drug accumulation, lower dose regimens may still be efficacious, yet associated with reduced toxicity.