Cytochrome P450 2E1 and 3A activities do not differ between Mexicans and European Americans.
OBJECTIVE
Population differences in the activity of various cytochrome P450 (CYP) enzymes have been demonstrated on the basis of either genetic or environmental determinants. Hispanics are a large demographic group both worldwide and within the United States; hence the possibility of differences in metabolism between one such group-Mexicans-and a European-derived population was determined with respect to CYP2E1 and CYP3A.


METHODS
Young healthy Mexican immigrants living in Los Angeles, Calif, who had maintained a traditional diet were compared with previously and identically studied groups of age-, sex-, and weight-matched European Americans who resided in middle Tennessee and ate a "western" diet (15 men and 15 women). In one study carried out in 15 women, the disposition of chlorzoxazone after an oral dose (250 mg) was compared. In the other investigation, all of the 15 subjects were men and received intravenous [(15)N(3)]-labeled midazolam (1 mg) and oral midazolam (2 mg) simultaneously to characterize the disposition of benzodiazepine in the two populations.


RESULTS
Plasma concentration-time profiles of chlorzoxazone and its 6-hydroxy metabolite and the 0- to 24-hour urinary recovery of the latter were not different between Mexicans and European Americans. This indicates that CYP2E1 activity is similar in the two populations. Similarly, no significant intergroup differences were noted in the plasma concentration-time profiles of midazolam after either intravenous or oral administration. Accordingly, CYP3A does not appear to be different between Mexicans and European Americans.


CONCLUSIONS
Similarity in the metabolism of chlorzoxazone between Mexicans and European Americans suggests that the risk associated with CYP2E1-mediated activation of procarcinogens is not different between these two populations. Likewise, the absence of any difference in the disposition of midazolam indicates that, from a pharmacokinetic standpoint, dosages of drugs metabolized by CYP3A need not be different between Mexicans and European Americans.
Poland
Russell A
RA
Department of Psychiatry, Research Center on the Psychobiology of Ethnicity, Harbor-UCLA Medical Center, Torrance, CA, USA.
Lin
Keh-Ming
KM
Nuccio
Cenci
C
Wilkinson
Grant R
GR
D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases; D002753:Chlorzoxazone / Q000493:pharmacokinetics; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism*; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005060:Europe; D005260:Female; D018565:Food-Drug Interactions / Q000502:physiology; D006801:Humans; D015141:Los Angeles; D008297:Male; D017058:Mexican Americans / Q000235:genetics; D008874:Midazolam / Q000493:pharmacokinetics; D008875:Middle Aged; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism*; D018709:Statistics, Nonparametric; D044465:White People / Q000235:genetics
D003577:Cytochrome P-450 Enzyme System; D019392:Cytochrome P-450 CYP2E1; D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; D010089:Oxidoreductases, N-Demethylating; D002753:Chlorzoxazone; D008874:Midazolam