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

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.

Pharmacokinetics and adverse reactions after a single dose of pentamidine in patients with Trypanosoma gambiense sleeping sickness.

“…In a previous study [8], similar fluctuations in plasma drug concentration curve during i.v. infusion were observed, and in another study [21] there were substantial deviations of mean concentrations during infusion which may reflect the same phenomenon as observed in this study. During the later part of the sampling period (i.e.…”

“…[12], in blood samples obtained at 1, 2, 4, 7, 14 and 29-34 days after pen-tamidine administration, showed that only three patients (2, 3 and 10) had uniformly detectable concentrations. The plasma phenobarbitone concentrations varied between 20 and 86 gmol l-1, except in patient 10 whose levels were in the range [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] ,umol 1-1 (the therapeutic range for treatment of convulsive disorders is 40-135 gmol l-l). A majority of the subjects were also given a single intramuscular injection of betamethasone (Diprostene®, ScheringPlough, Levallois-Perret, France).…”

Effects of Acute Intravenous Administration of Pentamidine, a Typical hERG-Trafficking Inhibitor, on the Cardiac Repolarization Process of Halothane-Anesthetized Dogs

“…administration of pentamidine, a hERG trafficking inhibitor (10,11), on the cardiac repolariza- tion process using the well-established halothaneanesthetized in vivo canine model (15 -17). Pentamidine is clinically administered by intramuscular injection and intravenous infusion over 2 h in a dose of 4 mg/kg a day, of which peak plasma concentrations have been reported to be 209 ng/ mL (0.4 μM) and 612 ng/mL (1 μM), respectively (20). In this study, we administered 1 mg/kg of pentamidine over 10 min followed by 3 mg/kg over 10 min with a pause of 20 min to better compare the cardiovascular effects of pentamidine with those of previously assessed drugs under the same experimental protocol as used in this study (15 -17).…”

Health hazard evaluation report: HETA-90-0330-2479, New York City Health and Hospitals Corporation, New York, New York.

“…The pentamidine level was analyzed according to a published method. 25 The limit of detection was 0.5 ng of pentamidine per ml of urine. The creatinine content of each specimen was also analyzed, and pentamidine results were corrected for dilution by dividing by the creatinine concentration, and were expressed as nanograms of pentamidine per milligram of creatinine (ng/mg).…”