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What is known and objective: Gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, exhibited a wide interindividual variability in pharmacokinetics. In the present study, we aimed to evaluate the impact of single‐nucleotide polymorphisms in the metabolizing enzymes and transporters on gefitinib disposition in healthy Chinese subjects. Methods: Fourteen single‐nucleotide polymorphisms, including polymorphisms of ATP‐binding cassette (ABC) transporters and cytochrome P450 enzymes, were genotyped by Sanger sequencing, and the concentration of gefitinib was measured by ultrafast liquid chromatography‐tandem mass spectrometry. The association between the pharmacokinetic parameters (peak plasma concentration [Cmax], time to reach Cmax, plasma half‐life, area under the concentration‐time curve from 0 to 168 hours [AUC(0‐168h)], AUC(0‐∞) and plasma clearance [CL/F]) and genotypes was evaluated using unpaired t test or Mann‐Whitney U test. A stepwise multiple linear regression analysis was applied to assess the relationships between multiple factors and gefitinib pharmacokinetics. Thirty‐nine healthy Chinese male subjects were enrolled in the pharmacokinetic study. Results and discussion: Subjects carrying an ABCG2 A allele (c.421CA + c.421AA genotypes) exhibited 33 and 37% increases in the mean gefitinib AUC(0‐168h) and AUC(0‐∞) values (P <.05), respectively, compared to that of subjects carrying wild‐type ABCG2 (c.421CC). Additionally, the mean CL/F of the c.421A allele carriers was 32% less than that of the c.421CC carriers (P <.05). No associations were found between polymorphisms in other metabolic enzymes or ABC transporters and gefitinib pharmacokinetics. What is new and conclusion: Our results suggested that a single‐nucleotide polymorphism in ABCG2 (c.421C>A) significantly affected the pharmacokinetics of gefitinib. Further studies are required to evaluate the effects of single‐nucleotide polymorphism on the pharmacokinetics, pharmacodynamics and toxicity of gefitinib. [ABSTRACT FROM AUTHOR]

What is known and objective: Nebivolol, a selective β1 adrenoreceptor antagonist, is predominantly metabolized by cytochrome P450 (CYP)2D6 and shows a wide interindividual variability in pharmacokinetics. The present study was conducted to evaluate the effects of the major CYP2D6 polymorphisms on nebivolol disposition in healthy Chinese volunteers. Methods: Twenty‐eight volunteers were enrolled and classified as CYP2D6*1/*1, CYP2D6*1/*10, CYP2D6*10/*10 and CYP2D6*5 carriers according to their genotypes. The concentration of nebivolol was determined by high‐performance liquid chromatography‐tandem mass spectrometry. The association between the pharmacokinetic parameters and genotypes was evaluated using the unpaired t test or analysis of variance. Results and discussion: We evaluated the effects of CYP2D6*5 and *10 polymorphism on the pharmacokinetics of nebivolol. Plasma nebivolol peak concentration and area under the curve (AUC(0‐48 h) and AUC(0‐∞)) were significantly higher in subjects with CYP2D6*5 and CYP2D6*10/*10 polymorphism than those in subjects with wild‐type CYP2D6 (CYP2D6*1/*1), whereas its plasma clearance was significantly lower in the CYP2D6*10/*10 and CYP2D6*5 carriers. No significant differences in the peak time and terminal half‐life of nebivolol were observed among CYP2D6*10/*10, CYP2D6*1/*1 and CYP2D6*5 carriers. What is new and conclusion: Both CYP2D6*5 and *10 polymorphism altered the pharmacokinetics of nebivolol in healthy Chinese volunteers. Further studies are required to investigate the effects of these single‐nucleotide polymorphisms on the pharmacokinetics, pharmacodynamics and toxicity of nebivolol. [ABSTRACT FROM AUTHOR]