I. Tantcheva-poor et al., Estimation of cytochrome P-450CYP1A2 activity in 863 healthy Caucasians using a saliva-based caffeine test, PHARMACOGEN, 9(2), 1999, pp. 131-144
A pronounced variability limits the usefulness of CYP1A2 phenotyping far dr
ug therapy, for evaluating liver function, and for assessing the role of th
is enzyme in carcinogenesis. To identify and quantify sources of this varia
tion, we estimated CYP1A2 activity in 863 healthy Caucasians using caffeine
clearance derived from saliva concentrations before and 5-7 h after a caff
eine test dose. Data from 786 individuals were eligible for evaluation (mea
n age 39 years, 415 women including 94 taking oral contraceptives, 401 non-
smokers). Overall geometric mean (geometric SD) caffeine clearance was 1.34
ml min(-1) kg b.w.(-1) (1.65). The effect of the following covariates was
evaluated by analysis of covariance: age, sex, oral contraceptives, body he
ight, body weight, body mass index, number of cigarettes smoked, tar exposu
re ham smoking, several indices of dietary caffeine consumption, intake of
sauerkraut, and country of residence (Germany, Bulgaria or Slovakia). Estim
ated changes relative to arbitrarily defined basal caffeine clearance (male
, nonsmoking, German resident) exerted by significant (P < 0.05) covariates
were: coffee, 1.45-fold per litre of coffee drunk daily; body mass index,
0.99-fold per kg m(-2); smoking, 1.22-fold, 1.47-fold, 1.66-fold, and 1.72-
fold for 1-5, 6-10, 11-20, and > 20 cigarettes smoked per day, respectively
; oral contraceptives, 0.72-fold; country of residence, 0.81-fold and 0.74-
fold for Bulgaria and Slovakia, respectively; female, 0.90-fold. These cova
riates explained 37% of overall variation. The 95% confidence interval of i
ndividual clearance was 0.46-2.20 times the predicted value. No relevant po
lymorphism was found for CYP1A2 activity when adjusted for covariate effect
s, Pharmacogenetics 9:131-144 (C) 1999 Lippincott Williams & Wilkins.