CYP2C9 allele frequency differences between populations of Mexican-Mestizo, Mexican-Tepehuano, and Spaniards.

Earlier we had found that the CYP2C9*2 allelic frequency was lower in Mexican-Americans living in California than in Spaniards (SP). This was assumed to be related to the low CYP2C9*2 and *3 allele frequencies in Orientals. This study was therefore aimed at analyzing whether there were also differences in CYP2C9 allele frequencies between Mexican-Tepehuanos (MT) and Mexican-Mestizos (MM) living in northwestern Mexico and SP. The CYP2C9*2 frequency was expected to be lower in the indigenous MT than in the two other groups, and lower in MM than in SP as in our earlier study. CYP2C9 genotypes and allele frequencies of two populations of healthy volunteers, MT (n=99) and MM (n=102), were compared with a population of SP (n=327). The data were also compared with our previously published population of Mestizo-Mexican-Americans (MA). The CYP2C9 genotypes among the studied populations were in equilibrium. The frequencies of CYP2C9*2 were 0.01, 0.07, 0.08, and 0.16 for MT, MM, MA, and SP subjects, respectively. In agreement with our hypothesis, CYP2C9*2 was significantly lower in the Mexican populations than in the SP (P<0.05), and among Mexicans in the MT than in the MM and MA groups (P<0.05), which presented similar frequencies. Moreover, the frequency of CYP2C9*3 was found to be lower (P<0.05) in MM (0.015) and MT (0.015) than in MA (0.06) and SP (0.08). Finally, the CYP2C9*6 allele was present just in one MM subject, and CYP2C9*4 and *5 were not found in the studied populations. Therefore, these findings add further evidence about CYP2C9 genetic diversity within Hispanic populations with regard to their ancestry. Considering that CYP2C9*2 and CYP2C9*3 alleles have altered catalytic activities relative to CYP2C9*1, the present data suggest the need for pharmacogenetic studies to optimize drug dosages in different populations.

Pharmacokinetic and nephrotoxic study of gentamicin in rabbits using a new dosage regimen.

Currently, in certain clinical situations there is an increasing trend towards using dosage regimens involving aminoglycoside antibiotics based on the administration of a single dose of the drug per day instead of administering the same amount in two or three administrations. The aim of the present study was to discover the pharmacokinetic profile and the nephrotoxic potential of this new form of administration in experimental animals receiving gentamicin. The study was conducted on two groups of rabbits, one of which received a single dose of the drug at 7 mg/kg i.v. and the other 7 mg/kg administered every 12 hours, allometrically equivalent to gentamicin dosing at 5 mg/kg every 24 hours to human subjects. The number of doses administered was 20. From the pharmacokinetic point of view, the results point to the existence of a significant degree of accumulation of the antibiotic in renal cortex as a result of the dosage regimen, no important modifications occurring in the pharmacokinetic parameters of gentamicin calculated from its plasma kinetics. This shows that the two compartment model employed predicts drug levels in accessible tissues but not in deep ones where gentamicin is accumulated for long periods of time. From the toxicological point of view, the treatment caused appreciable damage of the renal tubules during the first phases of the treatment which was not detectable from the serum creatinine levels or the kinetic behaviour of the aminoglycoside.