Pharmacokinetics of Tenofovir Alafenamide Fumarate and Tenofovir in the Chinese People: Effects of Non-Genetic Factors and Genetic Variations.

Abstract

Background: Tenofovir alafenamide fumarate (TAF) was approved for HBV treatment in China in 2018. Despite higher antiviral efficacy and less impact on renal function and bone mineral density, the pharmacokinetic profiles of TAF are highly variable. The objectives of this study were to investigate the pharmacokinetics of TAF in the Chinese population and explore the associations between TAF and genetic polymorphisms and non-genetic factors.

Patients and methods: A total of 64 healthy Chinese subjects aged 18~65 years old were planned to enroll. According to the dietary intake status, the subjects were divided into two groups (n = 32 per group). The concentrations of TAF and tenofovir were measured by HPLC-MS/MS, and the single-nucleotide polymorphisms were analyzed by MALDI-TOF MS.

Results: All the enrolled participants (18-35 years) completed the clinical trial study. Similar to the results reported in other ethnic populations, the pharmacokinetic profiles of TAF and tenofovir were highly variable in the Chinese people, and the HFHC diet can significantly increase the systemic exposure of TAF. We determined both HFHC diet and rs7311358 (SLCO1B3) genotypes were independently associated with TAF AUC _0-t , while HFHC diet, age and rs3740066 (ABCC2) variants were predictive of t_1/2 of tenofovir (P < 0.05). The subjects with the AA genotype in rs7311358 had significantly higher TAF AUC_0-t values (1.15 times) than those with a G allele, and the t_1/2 of tenofovir in the rs3740066 TT genotype group was 1.23 times longer than that of CC genotype group. Furthermore, there was a trend of higher TAF AUC and shorter tenofovir t_1/2 for the rs2032582 (ABCB1) T allele and rs3742106 (ABCC4) CC variant, respectively, although not statistically significant in the multiple linear regression analysis.

Conclusion: This study provided new evidence to suggest a critical link between both genetic and non-genetic factors and TAF pharmacokinetics in the Chinese people.