ABSTRACT
OBJECTIVES: To determine a population pharmacokinetic model of the antihelmintic drug, albendazole, and identify the factors influencing the pharmacokinetic parameters in patients with neurocysticercosis. METHODS: A prospective study was performed in 90 patients receiving 30 mg/kg/day of albendazole for 8 days. Blood samples were collected at steady state. Plasma concentrations of albendazole sulfoxide, the main active metabolite of albendazole, were determined by HPLC. The population pharmacokinetics analysis was performed using non-linear mixed-effect modeling (NONMEM). A one-compartment model with first order absorption and elimination was used. RESULTS: Body weight was included empirically on CL/F and V/F using an allometric relationship. Although none of the investigated covariates had a significant influence on the pharmacokinetic parameters of albendazole, the final model identified two subpopulations on the bioavailability parameter. One subpopulation comprising of 27% of the total population had a bioavailability of 28%, with the remaining subpopulation defined to have complete bioavailability. The CL/F and V/F for a standard 70 kg individual was determined to be 51.6 l/h and 4560 l, respectively. Interindividual variability in CL/F was 32%; the residual unexplained variability was 32%. CONCLUSIONS: The considerable variability reported in albendazole pharmacokinetics and plasma concentrations is likely due to issues related to bioavailability. With one-fourth of the population absorbing as little as 30% of the drug relative to others, low drug exposures might be responsible for treatment failures. Therapeutic drug monitoring may be warranted to optimize the eradication of the infecting parasite.
Subject(s)
Albendazole/pharmacokinetics , Anthelmintics/pharmacokinetics , Models, Biological , Neurocysticercosis/drug therapy , Adolescent , Adult , Aged , Albendazole/analogs & derivatives , Albendazole/therapeutic use , Anthelmintics/therapeutic use , Biological Availability , Chromatography, High Pressure Liquid , Drug Monitoring/methods , Female , Humans , Male , Middle Aged , Nonlinear Dynamics , Prospective Studies , Young AdultABSTRACT
Thirty-six patients with subarachnoid and intraventricular cysticercosis were randomly assigned to receive albendazole at 15 or 30 mg/kg/day plus dexamethasone for 8 days. Results favored a higher dose, with larger cyst reduction on MRI at 90 and 180 days and higher albendazole sulfoxide levels in plasma. An albendazole course at 30 mg/kg/day combined with corticosteroids is safe and more effective than the usual dose. A single treatment was insufficient in intraventricular and giant cysts.
