PHARMACOKINETICS OF MELARSOPROL IN UNINFECTED VERVET MONKEYS

The level of the trypanocidal drug melarsoprol was determined in serum and cerebrospinal fluid (CSF) of six healthy vervet monkeys after int ravenous application of the drug following a standard treatment schedu le and a recently suggested alternative protocol. The maximum serum le vels measured were about 3 mu g/ml. A three-compartment model was used to analyze the serum data. The mean residence time calculated for mel arsoprol in serum was 18 h, the volume of distribution was 3.6 1/kg an d the clearance was 3.5 ml/minkg. In the CSF the drug levels were gen erally very low, not exceeding 55 ng/ml, and the adaptation of the dru g levels was found to be very slow. The comparison of the drug concent rations required to eliminate trypanosomes in vitro and the drug conce ntrations reached in the CSF during treatment revealed that the latter might be insufficient in some cases to eliminate all trypanosomes fro m this site. The peak serum levels during alternative application of t he drug were lower compared to those during empirical treatment. No ev idence for drug cumulation in the body was found. The results of this study are compared with recent pharmacokinetic data from human patient s, and discussed in the context of the problem of relapses and reactiv e encephalopathy occurring after treatment of sleeping sickness.