Eflornithine concentrations in serum and cerebrospinal fluid of 63 patients treated for Trypanosoma brucei gambiense sleeping sickness
- 1 July 1993
- journal article
- Published by Oxford University Press (OUP) in Transactions of the Royal Society of Tropical Medicine and Hygiene
- Vol. 87 (4), 473-477
- https://doi.org/10.1016/0035-9203(93)90044-q
Abstract
Eflornithine (difluoromethylornithine, DFMO) has recently been approved for the treatment of Trypanosoma brucei gambiense trypanosomiasis. Treatment failures have been infrequent but have occurred among patients treated with oral DFMO only, and among children. To investigate the higher frequency of failures observed in young patients, DFMO trough concentrations in serum and cerebrospinal fluid (CSF) were measured at the end of treatment in 13 children and 50 adults who had received 200 mg/kg intravenously every 12 h for 14 d. Mean DFMO concentration in CSF was significantly lower among children aged less than 12 years when compared to older patients (25·1 vs 68·9 nmol/mL, P < 0·001). Mean serum concentration was also lower in children (49·2 vs 87·5 nmol/mL, P = 0·03). Among patients who received DFMO as initial therapy for sleeping sickness, the mean CSF/serum ratio was lower in children (0·41 vs 0·91, P < 0·005). The 3 patients who failed DFMO treatment had CSF trough concentrations around or below 50 nmol/mL. Convulsions and anaemia were associated with higher drug levels and previous therapy with melarsoprol. The lower CSF drug concentrations observed in children could result from higher renal clearance and different CSF pharmacokinetics of DFMO in that age group. To avoid treatment failures, a 6-hourly regimen as well as higher DFMO dosage based on body surface area rather than on weight are recommended for children.Keywords
This publication has 15 references indexed in Scilit:
- Efficacy and toxicity of eflornithine for treatment of Trypanosoma brucei gambiense sleeping sicknessThe Lancet, 1992
- New drug for trypanosomiasisThe Lancet, 1991
- Clinical Pharmacokinetics in Infants and Children A ReappraisalClinical Pharmacokinetics, 1989
- Treatment of Human Late Stage Gambiense Trypanosomiasis with α-Difluoromethylornithine (Eflornithine): Efficacy and Tolerance in 14 Cases in Côte D'IvoireThe American Journal of Tropical Medicine and Hygiene, 1987
- Catalytic irreversible inhibition of Trypanosoma brucei brucei ornithine decarboxylase by substrate and product analogs and their effects on murine trypanosomiasisBiochemical Pharmacology, 1985
- Brain, CSF, and tumor pharmacokinetics of ?-difluoromethylornithine in rats and dogsCancer Chemotherapy and Pharmacology, 1983
- Polyamine metabolism and functionAmerican Journal of Physiology-Cell Physiology, 1982
- Kinetics of α-difluoromethylornithine: An irreversible inhibitor of ornithine decarboxylaseClinical Pharmacology & Therapeutics, 1981
- Assay of α-difluoromethylornithine in body fluids and tissues by automatic amino-acid analysisJournal of Chromatography B: Biomedical Sciences and Applications, 1981
- Polyamine Metabolism: A Potential Therapeutic Target in TrypanosomesScience, 1980