Population pharmacokinetics of albendazole in patients with neurocysticercosis.
OBJECTIVE
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.
Castro
N
N
Instituto Nacional de Neurologia y Neurocirugía, Universidad Nacional Autónoma de México, México City, Mexico.
Márquez-Caraveo
C
C
Brundage
R C
RC
González-Esquivel
D
D
Suárez
A M
AM
Góngora
F
F
Jara
A
A
Urizar
J
J
Lanao
J M
JM
Jung
H
H
D000293:Adolescent; D000328:Adult; D000368:Aged; D015766:Albendazole / Q000031:analogs & derivatives / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000871:Anthelmintics / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D020019:Neurocysticercosis / Q000188:drug therapy*; D017711:Nonlinear Dynamics; D011446:Prospective Studies; D055815:Young Adult
D000871:Anthelmintics; D015766:Albendazole; C027186:albendazole sulfoxide