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. 2012 Jan;13(1):113-21.
doi: 10.2217/pgs.11.132. Epub 2011 Nov 23.

Exploration of CYP450 and drug transporter genotypes and correlations with nevirapine exposure in Malawians

Kevin C Brown  1 , Mina C Hosseinipour, Janelle M Hoskins, Ranjit K Thirumaran, Hsiao-Chuan Tien, Ralf Weigel, Jean Tauzie, Ida Shumba, Jatinder K Lamba, Erin G Schuetz, Howard L McLeod, Angela D M Kashuba, Amanda H Corbett
Affiliations

Exploration of CYP450 and drug transporter genotypes and correlations with nevirapine exposure in Malawians

Kevin C Brown et al. Pharmacogenomics. 2012 Jan.

Abstract

Aim: Genetic polymorphisms have the potential to influence drug metabolism and vary among ethnic groups. This study evaluated the correlation of genetic polymorphisms with nevirapine pharmacokinetics exposure in Malawians.

Materials & methods: CYP450 2B6, 2D6, 3A4 and 3A5, ABCB1 and constitutive androstane receptor and pregnane X receptor, were analyzed for polymorphisms in 26 subjects.

Results: Allele frequencies (variant) were: CYP2B6 514G>T (0.31) CYP2D6*4 (0.02); CYP2D6*17 (0.35); CYP3A4*1B (0.77); CYP3A5*3 (0.25); ABCB1 2677G>T (0.0), ABCB1 3435C>T (0.21), NR1I3 13711152T>C (0.02), NR1I2 44477T>C (0.10), NR1I2 63396C>T (0.33), NR1I2 6-bp indel (del: 0.17). CYP2B6 516G>T (non-wild-type/wild-type) correlated with nevirapine pharmacokinetic parameters; geometric mean ratios (95% CI): 1.75 (1.27-2.40) for area under the concentration time curve (AUC)(0-12 h), 1.58 (1.03-2.42) for C(0), and 0.53 (0.31-0.91) for clearance. In a multivariable model, nevirapine AUC increased by 1.5% per year of age (p < 0.0001), CYP2B6 516 T allele increased AUC by 92% (p < 0.0001), and CYP3A5*3 decreased AUC by 31% (p = 0.0027).

Conclusion: Allele frequencies were similar to other sub-Saharan African populations. The T allele for CYP2B6 516 was significantly associated with nevirapine exposure.

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Figures

Figure 1
Figure 1. Weight-adjusted clearance versus CYP2D6*17 genotype (*17 = T allele) in the pediatric group and adult group
(A) Pediatric group, (B) Adult group. CL: Clearance.
See this image and copyright information in PMC

References

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Websites

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