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>