Use of a specific and sensitive assay to determine pentamidine pharmacokinetics in patients with AIDS

J Infect Dis. 1986 Dec;154(6):923-9. doi: 10.1093/infdis/154.6.923.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acquired Immunodeficiency Syndrome / metabolism*
  • Adult
  • Amidines / metabolism*
  • Chromatography, High Pressure Liquid
  • Creatinine / blood
  • Homosexuality
  • Humans
  • Injections, Intramuscular
  • Injections, Intravenous
  • Male
  • Middle Aged
  • Pentamidine / blood
  • Pentamidine / metabolism*
  • Pentamidine / urine
  • Pneumonia, Pneumocystis / metabolism

Substances

  • Amidines
  • Pentamidine
  • Creatinine