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

1 Plasma concentrations of pentamidine were measured up to 1-8 months after a single 2 h i.v. infusion of 3.0 to 4.8 mg kg(-1) pentamidine isethionate in 11 patients with late stage Trypanosoma gambiense sleeping sickness. 2 Maximum plasma drug concentrations varied between 713 and 2461 nmol l(-1) After termination of infusion, a rapid distribution phase over 10 min was followed by a slower distribution phase and an elimination phase prolonged over weeks to months. 3 The 'terminal' elimination rate constant could be determined in six patients and subsequent kinetic calculations showed a three to fourfold variation in plasma clearance and 'terminal' half-life (median 1126 (range 553-2036) mi min(-1) and 265 (107-446) h, respectively). The median apparent volume of distribution (V-ss) was 11 850 1. Renal clearance accounted for a median of 11% of total plasma clearance, indicating that metabolism is a major route of pentamidine elimination in man. 4 Side effects were few and mild and a slight or moderate decrease in blood pressure was the most common registered adverse reaction observed in four subjects. 5 The prolonged elimination of pentamidine seems inconsistent with the present recommended dosage regimen of pentamidine for treatment of trypanosomiasis of 7 to 10 parenteral doses given once daily or every second day.