Publication Cover
Xenobiotica
the fate of foreign compounds in biological systems
Volume 46, 2016 - Issue 9
508
Views
10
CrossRef citations to date
0
Altmetric
Xenobiotic Transporters

Mixed effects of OATP1B1, BCRP and NTCP polymorphisms on the population pharmacokinetics of pravastatin in healthy volunteers

, , &
Pages 841-849 | Received 21 Oct 2015, Accepted 08 Dec 2015, Published online: 08 Jan 2016
 

Abstract

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.

2. Genetic polymorphisms of rs4149056 (OATP1B1) and rs2306283 (OATP1B1) were found to be associated with a significant (p < 0.01) decrease in the apparent clearance from the central compartment (CL/F), while rs2296651 (NTCP) increased CL/F to a significant degree (p < 0.01). The combination of these three polymorphisms reduced the inter-individual variability of CL/F by 78.8%.

3. There was minimal effect of rs2231137 (BCRP) and rs2231142 (BCRP) on pravastatin pharmacokinetics (0.01 < p < 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 (p > 0.05).

4. The current data suggest that the combination of rs4149056, rs2306283 and rs2296651 polymorphisms is an important determinant of pravastatin pharmacokinetics.

Acknowledgements

The authors gratefully acknowledge the assistance of Mrs. S. Ma from the Second Affiliated Hospital of Jilin University, China, for her help in the pharmacokinetic experiments.

Declaration of interest

This work was supported by the National Natural Science Foundation of China (No. 81373367). The authors declare no conflict of interest.

Supplementary materials available on line

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.