Pharmacokinetic Model for Losartan Administered to Young Mexican Healthy Volunteers.
Carlos Hoyo-Vadillo and Hector González M.
Cinvestav, Mexico
Objectives: To evaluate the pharmacokinetics of Losartan (100 mg) in a Young Healthy Volunteers Mexican Population.
Methods: Eighty two healthy volunteers of both genders were enroled at Guadalajara City (Western of Mexico). Dose was 100 mg given at the morning after overnight fast. NONMEM VI was used on a laptop running Vista. Basic for Nonmem (presented last year at Page at Marseille) was used as an auxiliary tool. 296 runs were evalauted to look for combinations of exp(eta) and different initial values. ADVAN4 TRANS 3 was employed. F1=EXP(ETA(1)) was incluided. Summary tables were examined at Microsoft excel. xpose4 was employed to evaluate the models.
Results: Minimal objective function was 8412. Lag time was not included. Clearance was 89.9 +- 4.5 L/h, Volume of distribution was 103 +-10.0 L, absoption constant was 2.23+_0.24 h-1, intercompartmental clearance was 11.4 +- 1.2 L/h. This clearance was greater then the reported for Caucasian populions, which can be due to the low rate of CYP2C9 mutations on Mexican population. But enviromental factors can also play a role.
References:
[1]. Yasar et al. Pharmacokinetics of losartan and its metabolite E-3174 in relation to the CYP2C9 genotype. Clinical Pharmacology & Therapeutics (2002) 71, 89–98.
[2]. LLerena et al. Lower frequency of CYP2C9*2 in Mexican-Americans compared to Spaniards. The Pharmacogenomics Journal (2004) 4, 403–406.