IVERMECTIN DISTRIBUTION IN THE PLASMA AND TISSUES OF PATIENTS INFECTED WITH ONCHOCERCA-VOLVULUS

Objective: To determine the distribution of ivermectin in plasma and t issues of onchocerciasis patients following a single oral dose of 150 mu g kg(-1). Setting. Medical Department at Soba University Hospital, Khartoum. Patients: Twenty five patients and fourteen healthy voluntee rs. Methods: Serial blood samples were obtained from both groups. Tiss ue samples were removed from various patients as full thickness skin p unch biopsies or during nodulectomy. Ivermectin concentration was dete rmined by radioimmunoassay. Results: The plasma pharmacokinetic variab les for patients were maximum plasma concentration 52.0 ng ml(-1) time to achieve maximum concentration, 5.2 h.; elimination half life, 35.0 h; and the area under the plasma concentration curve versus time, 285 2 ng . h ml(-1). In healthy volunteers, the plasma ivermectin distribu tion was similar to that in patients, and both groups showed a tendenc y for a second rise in plasma concentration of the drug suggestive of enterohepatic recirculation. Ivermectin was detected in tissues obtain ed from patients. Fat showed the highest and most persistent levels, w hilst values for skin, nodular tissues, and worms were comparable. Sub cutaneous fascia contained the lowest concentrations. Conclusion: Infe ction with O. volvulus does not affect the pharmacokinetics of ivermec tin, and filarial infected tissues and parasites themselves do take up the drug. There may be prolonged retention of ivermectin because of d epot formation in fat tissue.