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.
Instituto Nacional de Neurologia y Neurocirugía, Universidad Nacional Autónoma de México, México City, Mexico.
N
N
Castro
C
C
Márquez-Caraveo
R C
RC
Brundage
D
D
González-Esquivel
A M
AM
Suárez
F
F
Góngora
A
A
Jara
J
J
Urizar
J M
JM
Lanao
H
H
Jung
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