Genetic polymorphisms of CYP2C9 markedly affect the pharmacokinetics of both glyburide and glimepiride. The influence of the CYP2C9*3 variant allele on glyburide and glimepiride pharmacokinetics may be clinically significant.

Cyclophosphamide (CP), a widely used cytostatic, is metabolized by polymorphic drug metabolizing enzymes particularly cytochrome P450 (CYP) enzymes. Its side effects and clinical efficacy exhibit a broad interindividual variability, which might be due to differences in pharmacokinetics. CP-kinetics were determined in 60 patients using a global and a population pharmacokinetic model considering functionally relevant polymorphisms of CYP2B6, CYP2C9, CYP2C19, CYP3A5, and GSTA1. Moreover, metabolic ratios were calculated for selected CP metabolites, analyzed by 31 P-NMR-spectroscopy. Analysis of variance revealed that the CYP2C19*2 genotype influenced significantly pharmacokinetics of CP at doses p1000 mg/m 2 , whereas there was no evidence of an association of other genotypes to CP elimination or clearance. Mean (7SD) CP elimination constants k e (h À1 ) were 0.10970.025 in 44 CYP2C19*1/*1 subjects, 0.08870.018 in 13 CYP2C19*1/*2, and 0.07670.014 in three inactive CYP2C19*2/*2 carriers (P ¼ 0.009). At CP doses higher than 1000 mg/m 2 , a significantly increase of elimination was observed (P ¼ 0.001), possibly due to CYP induction. Further studies should link these findings with the clinical outcome.

The data suggest that the slow acetylator phenotype may be associated with a higher risk of periodontitis, especially in smokers. Possible explanations regarding the mechanism are discussed; however, such attempts are highly speculative at this time.