Pharmacokinetic investigations in patients from northern Angola refractoryto melarsoprol treatment

Melarsoprol, an organo-arsenical drug, has been the drug of choice for late -stage trypanosomiasis for 50 years. Because of the lack of alternatives an y abatement of this medication will have a dramatic negative impact on the perspectives for patients. As a large number of patients refractory to mela rsoprol treatment was recently reported from northern Uganda and northern A ngola, we investigated in northern Angola whether interpatient pharmacokine tic differences influence the outcome of melarsoprol treatment. Drug levels were determined by a biological assay in serum and cerebrospinal fluid (CS F) of 22 patients. Nine patients could be successfully treated, eight were refractory and the outcome was unclear or no adequate follow-up information was available for five patients. No differences in the pharmacokinetic par ameters (maximum serum concentration C-max, half-life t(1/2 beta), total cl earance C-L and the Volume of distribution V-ss) could be detected between the groups. Serum and CSF concentrations for all patients were in the expec ted range. This result indicates that other underlying factors are responsi ble far treatment failures.