Effect of SLCO1B1*15 on Pravastatin Pharmacokinetics: A Systematic Review and Meta-analysis
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Background and objective: Pravastatin has been shown to have favorable risk-benefit profile when it isadministered to hypercholesterolemic subjects to prevent cardiovascular events. However, subjects with impairedOATP1B1 activity may be more susceptible to pravastatin-induced muscle toxicity than subjects with normalOATP1B1 activity. A systematic review was conducted to evaluate the effect of SLCO1B1 genetic polymorphismon pharmacokinetics of pravastatin. Method: Medline® and Embase® were searched for relevant studies until July2013. The search terms used were pravastatin AND (SLCO1B1 OR OATP1B1 OR LST1 OR SLC21A6) AND(gene OR genetic* OR genomic* OR pharmacogenet* OR pharmacogenom* OR polymorph*). Results: A metaanalysisof the area under the concentration-time curve (AUC) of pravastatin in SLCO1B1*15 and SLCO1B1*1a/*1a was conducted. Five studies met all the inclusion criteria and methodological requirements. There was no statisticallysignificant difference in the AUC value between SLCO1B1*15 and SLCO1B1*1a/*1a (p=0.728). However,SLCO1B1*15 participants exhibited significantly higher AUC values than SLCO1B1*1b/*1b carriers (p<0.001). In case of SLCO1B1*15*15 carriers, they had significantly higher AUC value than SLCO1B1*1a/*1a subjects(p=0.002). Lastly, compared with to the subjects of SLCO1B1*1a/*1a, the carriers of heterozygous SLCO1B1*15increased the AUC value of pravastatin statistically significantly in Asian population (p=0.014). Conclusion: Thepresent meta-analysis suggests that subjects with SLCO1B1*15 are associated with increased AUC of pravastatin.
Abstract
Background and objective: Pravastatin has been shown to have favorable risk-benefit profile when it isadministered to hypercholesterolemic subjects to prevent cardiovascular events. However, subjects with impairedOATP1B1 activity may be more susceptible to pravastatin-induced muscle toxicity than subjects with normalOATP1B1 activity. A systematic review was conducted to evaluate the effect of SLCO1B1 genetic polymorphismon pharmacokinetics of pravastatin. Method: Medline® and Embase® were searched for relevant studies until July2013. The search terms used were pravastatin AND (SLCO1B1 OR OATP1B1 OR LST1 OR SLC21A6) AND(gene OR genetic* OR genomic* OR pharmacogenet* OR pharmacogenom* OR polymorph*). Results: A metaanalysisof the area under the concentration-time curve (AUC) of pravastatin in SLCO1B1*15 and SLCO1B1*1a/*1a was conducted. Five studies met all the inclusion criteria and methodological requirements. There was no statisticallysignificant difference in the AUC value between SLCO1B1*15 and SLCO1B1*1a/*1a (p=0.728). However,SLCO1B1*15 participants exhibited significantly higher AUC values than SLCO1B1*1b/*1b carriers (p<0.001). In case of SLCO1B1*15*15 carriers, they had significantly higher AUC value than SLCO1B1*1a/*1a subjects(p=0.002). Lastly, compared with to the subjects of SLCO1B1*1a/*1a, the carriers of heterozygous SLCO1B1*15increased the AUC value of pravastatin statistically significantly in Asian population (p=0.014). Conclusion: Thepresent meta-analysis suggests that subjects with SLCO1B1*15 are associated with increased AUC of pravastatin.
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