10.6084/m9.figshare.1632778
Xue-Feng Lu
Xue-Feng
Lu
Yang Zhou
Yang
Zhou
Kai-Shun Bi
Kai-Shun
Bi
Xiao-Hui Chen
Xiao-Hui
Chen
Mixed effects of OATP1B1, BCRP and NTCP polymorphisms on the population pharmacokinetics of pravastatin in healthy volunteers
Taylor & Francis Group
2016
pravastatin population pharmacokinetics
pravastatin pharmacokinetics
OATP 1B BCRP
OATP 1B rs 1061018
plasma pravastatin concentrations
volunteers 1. Pravastatin
NTCP
2. Genetic polymorphisms
NONMEM
OATP 1B
CL
rs 2296651 polymorphisms
2016-01-11 09:16:57
Journal contribution
https://tandf.figshare.com/articles/journal_contribution/Mixed_effects_of_OATP1B1_BCRP_and_NTCP_polymorphisms_on_the_population_pharmacokinetics_of_pravastatin_in_healthy_volunteers/1632778
<p>1. Pravastatin is a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor used for the treatment of hyperlipidaemia. This study aims to investigate the effects of genetic polymorphisms in OATP1B1, BCRP and NTCP on pravastatin population pharmacokinetics in healthy Chinese volunteers using a non-linear mixed-effect modelling (NONMEM) approach. A two-compartment model with a first-order absorption and elimination described plasma pravastatin concentrations well.</p> <p>2. Genetic polymorphisms of rs4149056 (OATP1B1) and rs2306283 (OATP1B1) were found to be associated with a significant (<i>p</i> < 0.01) decrease in the apparent clearance from the central compartment (CL/<i>F</i>), while rs2296651 (NTCP) increased CL/<i>F</i> to a significant degree (<i>p</i> < 0.01). The combination of these three polymorphisms reduced the inter-individual variability of CL/<i>F</i> by 78.8%.</p> <p>3. There was minimal effect of rs2231137 (BCRP) and rs2231142 (BCRP) on pravastatin pharmacokinetics (0.01 < <i>p</i> < 0.05), whereas rs11045819 (OATP1B1), rs1061018 (BCRP) and rs61745930 (NTCP) genotypes do not appear to be associated with pravastatin pharmacokinetics based on the population model (<i>p</i> > 0.05).</p> <p>4. The current data suggest that the combination of rs4149056, rs2306283 and rs2296651 polymorphisms is an important determinant of pravastatin pharmacokinetics.</p>