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Use of a Specific and Sensitive Assay to Determine Pentamidine Pharmacokinetics in Patients with Aids

John E. Conte Jr., Robert A. Upton, Roger T. Phelps, Constance B. Wofsy, Elisabeth Zurlinden and Emil T. Lin
The Journal of Infectious Diseases
Vol. 154, No. 6 (Dec., 1986), pp. 923-929
Published by: Oxford University Press
Stable URL: http://www.jstor.org/stable/30104974
Page Count: 7
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Use of a Specific and Sensitive Assay to Determine Pentamidine Pharmacokinetics in Patients with Aids
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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 <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 S.D% 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.

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