Population pharmacokinetics of albendazole in patients with neurocysticercosis.

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.

Albendazole trial at 15 or 30 mg/kg/day for subarachnoid and intraventricular cysticercosis.

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.

Clinical pharmacokinetics of albendazole in children with neurocysticercosis.

The pharmacokinetics of albendazole sulphoxide, the main metabolite of albendazole, were studied in eight children with brain cysticercosis. Albendazole was given as a single oral dose of 15 mg per kg body weight (Zentel suspension; Smith Kline & Beecham, Philadelphia, PA). Blood samples were taken during 24 h and analyzed by high performance liquid chromatography. Plasma levels showed great interindividual variation. Maximum plasma levels for albendazole sulphoxide ranged from 0.2-1.0 microg/mL. A double peak was found in four children. The half-life for albendazole sulphoxide was from 2.3-8.3 hours and mean residence time values were from 5. 1-13.6 hours. These values are shorter than those found in adults. The results suggest that when treating children with neurocysticercosis, albendazole should be administered three times a day rather than twice daily as is currently done in Mexico.

Sensitive high-performance liquid chromatographic assay for praziquantel in plasma, urine and liver homogenates.

A high-performance liquid chromatographic method for the determination of praziquantel in plasma, urine and rat liver homogenates has been developed. It requires 2 ml of biological fluid, an extraction using Sep-Pak cartridges, a 0.05 M phosphate buffer solution (pH 5.0) for equilibrating and washing and ethyl acetate-diisopropyl ether for drug elution. The analysis was performed on an Ultrasphere ODS C18 column with a mobile phase of acetonitrile-water with ultraviolet detection at 217 nm. The results showed that the assay is sensitive (31.2 ng/ml), linear between 0.125 and 4.0 micrograms/ml, precise (coefficient of variation = 10%) and selective with other drugs currently administered with praziquantel.

Pharmacokinetic comparison of two albendazole dosage regimens in patients with neurocysticercosis.

To evaluate two different dosage regimens for albendazole (7.5 mg/kg twice a day or 5.0 mg/kg three times a day), a study was performed in 10 patients with a diagnosis of parenchymal brain cysticercosis. Each patient received both regimens sequentially according to a randomized, crossover design. Blood and urine samples were taken once the drug steady state had been reached. Plasma levels of albendazole sulfoxide at steady state were determined using a HPLC method. In spite of a great intersubject variability observed with both regimens in the area under the curve (AUC) and in the minimum steady-state plasma concentration (Cp min ss), no statistically significant differences were found in these parameters. We suggest that a regimen of 7.5 mg/kg every 12 h can favorably replace the currently used regimen of 5 mg/kg every 8 h.