Pharmacology: Pharmacodynamics: Mechanism of action: Pentamidine isethionate exhibits antiprotozoal activity against Pneumocystis carinii, Leishmania and some species of Trypanosoma.
The exact mechanism of antiprotozoal action of pentamidine has not been fully elucidated. Several mechanisms of action may be involved, and the role of the mechanism(s) may vary among the different types of protozoa (e.g. trypanosome, sporozoons). Most information on the antiprotozoal activity of pentamidine has been derived from studies involving trypanosomes. In vitro studies indicate that the drug interferes with nuclear metabolism.
Clinical trials: No data available.
Pharmacokinetics: Limited information is available concerning the pharmacokinetics of pentamidine isethionate.
Absorption: Following a single 4 mg/kg IV dose of pentamidine isethionate (given as a 2 hour infusion), peak plasma pentamidine concentrations averaged 612 nanogram/mL after completion of the IV infusion.
Distribution: Distribution of pentamidine into human body tissues and fluids has not been well characterised, but the drug appears to be rapidly and extensively distributed and/or bound to tissues. Pentamidine has a distribution half-life of 5 to 15 minutes after intravenous administration. Following parenteral administration, highest concentrations have been found in the liver, followed by the kidneys, adrenals, spleen, lungs and pancreas. Pentamidine penetrates the CNS only very poorly after prolonged therapy.
In vitro, pentamidine is reportedly 69% bound to serum proteins.
It is not known whether pentamidine isethionate crosses the placenta or is distributed into breast milk.
Excretion: Little is known about the elimination in humans. Plasma concentrations of pentamidine have been found to decline in a biphasic manner following a single IV infusion in patients with normal renal function. The mean elimination half-life was found to be 18 minutes in the initial phase and 6.4 hours in the terminal phase. Pentamidine appears to be eliminated very slowly from tissues in which the drug principally accumulates (e.g. liver, lungs). The half-life of pentamidine may be prolonged in patients with impaired renal function, however no correlation between renal function and plasma clearance of pentamidine has been found. It is not known if the drug is excreted in faeces.
Only a small amount (approximately 6%) of the administered dose is excreted unchanged in the urine over a 15 day period.
Following a single 4 mg/kg IV dose of pentamidine isethionate in patients with AIDS or pneumocystis pneumonia who had normal renal function, about 2.5 to 5% of the dose was excreted in urine as unchanged drug over 24 hours, mainly within the first 8 hours after administration. Similar amounts (about 1 to 4% of the dose) were also excreted in urine as unchanged drug in 24 hours in patients with mild to moderate renal impairment.
Limited data suggest that pentamidine is not appreciably removed by haemodialysis or peritoneal dialysis.
Toxicology: Preclinical safety data: Genotoxicity: No data available.
Carcinogenicity: No data available.
Microbiology: Pentamidine isethionate exhibits antiprotozoal activity against Pneumocystis carinii, Leishmania and some species of Trypanosoma.