The impact of SLCO1B1 polymorphisms on the plasma concentration of lopinavir and ritonavir in HIV-infected men
Article first published online: 22 SEP 2009
© 2010 The Authors. Journal compilation © 2010 The British Pharmacological Society
British Journal of Clinical Pharmacology
Volume 69, Issue 1, pages 95–98, January 2010
How to Cite
Kohlrausch, F. B., De Cássia Estrela, R., Barroso, P. F. and Suarez-Kurtz, G. (2010), The impact of SLCO1B1 polymorphisms on the plasma concentration of lopinavir and ritonavir in HIV-infected men. British Journal of Clinical Pharmacology, 69: 95–98. doi: 10.1111/j.1365-2125.2009.03551.x
- Issue published online: 23 DEC 2009
- Article first published online: 22 SEP 2009
- Received 22 May 2009Accepted17 August 2009
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT
• There is large interindividual variability in the pharmacokinetics of protease inhibitors (PIs) among human immunodeficiency virus (HIV)-infected individuals under highly active antiretroviral therapy.
• Protease inhibitor have been recently reported to be substrates of the SLCO1B1/OATP1 drug transporter.
• A single nucleotide polymorphism (SNP) in the SLCO1B1 gene (521TC) was associated with plasma levels of lopinavir in HIV-infected individuals.
WHAT THIS STUDY ADDS
• Data on the impact of three SLCO1B1 SNPs (521TC, 388AG, 463CA) on the trough plasma concentration of lopinavir and ritonavir in a cohort of 99 adult HIV-infected Brazilian men under stable highly active antiretroviral therapy.
• Evidence that carriers of the 521C allele display significantly higher lopinavir, but not ritonavir plasma concentrations relative to the wild-type TT genotype.
• No effect of either 388AG or 463CA SNPs on lopinavir or ritonavir plasma concentrations.
• Further studies are required to confirm the clinical significance of the association between the SLCO1B1521TC polymorphism and lopinavir pharmacokinetics.
AIMS To investigate possible associations between three SLCO1B1 single nucleotide polymorphisms (388AG, 463CA, 521TC) and lopinavir/ritonavir plasma concentrations.
METHODS The study included 99 human immunodeficiency virus-infected men on stable highly active antiretroviral therapy containing lopinavir/ritonavir. Trough concentrations of lopinavir and ritonavir in plasma were quantified using liquid chromatography–tandem mass spectrometry. Genotyping of SLCO1B1388AG, 463CA and 521TC polymorphisms was performed by allelic discrimination using real-time polymerase chain reaction.
RESULTS The trough concentration of lopinavir in plasma is significantly associated with SLCO1B1521TC genotypes (P= 0.03). There is a significant trend for increasing concentrations of lopinavir from TT to TC to CC genotypes (P= 0.02). Carriers of the 521C allele display significantly higher lopinavir plasma concentrations relative to the wild-type TT genotype (P= 0.03).
CONCLUSIONS Reduced uptake of lopinavir by hepatocytes in carriers of the 521C allele may account for these results, but further studies to confirm the clinical importance of SLCO1B1 polymorphisms in lopinavir pharmacokinetics are warranted.