Pharmacokinetic investigations in patients from northern Angola refractory to melarsoprol treatment

• Published in: Tropical medicine & international health Vol. 6; no. 5; pp. 412 - 420
• Main Authors: Burri, C., Keiser, J.
• Format: Journal Article
• Language: English
• Published: Oxford UK Blackwell Science Ltd 01.05.2001
• Subjects: Adolescent; Adult; Angola; Angola - epidemiology; Animals; Drug Administration Schedule; drug levels; Drug Monitoring; Drug Resistance; Female; Follow-Up Studies; Humans; Male; melarsoprol; Melarsoprol - administration & dosage; Melarsoprol - metabolism; Melarsoprol - pharmacokinetics; Middle Aged; pharmacokinetics; Serotyping; Severity of Illness Index; sleeping sickness; Treatment Failure; Trypanocidal Agents - administration & dosage; Trypanocidal Agents - metabolism; Trypanocidal Agents - pharmacokinetics; Trypanosoma brucei gambiense - classification; Trypanosoma brucei gambiense - genetics; trypanosomes; trypanosomiasis; Trypanosomiasis, African - drug therapy; Trypanosomiasis, African - epidemiology; Trypanosomiasis, African - metabolism; Trypanosomiasis, African - parasitology; Angola
• ISSN: 1360-2276; 1365-3156
• DOI: 10.1046/j.1365-3156.2001.00725.x

Melarsoprol, an organo‐arsenical drug, has been the drug of choice for late‐stage trypanosomiasis for 50 years. Because of the lack of alternatives any abatement of this medication will have a dramatic negative impact on the perspectives for patients. As a large number of patients refractory to melarsoprol treatment was recently reported from northern Uganda and northern Angola, we investigated in northern Angola whether interpatient pharmacokinetic differences influence the outcome of melarsoprol treatment. Drug levels were determined by a biological assay in serum and cerebrospinal fluid (CSF) 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 parameters (maximum serum concentration Cmax, half‐life t1/2β, total clearance CL and the volume of distribution Vss) could be detected between the groups. Serum and CSF concentrations for all patients were in the expected range. This result indicates that other underlying factors are responsible for treatment failures.