Clinical conundrums involving statin drug-drug interactions

Lamprecht, Donald G.; Saseen, Joseph J.; Shaw, P.W.

doi:10.1016/j.pcad.2022.11.002

Cited by 4 publications

(4 citation statements)

References 42 publications

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“…Currently, there are seven statins (rosuvastatin, atorvastatin, simvastatin, pitavastatin, lovastatin, pravastatin, and fluvastatin) that are readily available and have been proven to be well tolerated 5 . Although statins are generally considered safe, their systemic exposure may be influenced by drug–drug interactions (DDI), which may increase the risk of statin-associated muscle symptoms (SAMS) 10 , 11 . These interactions are predominantly facilitated by metabolic enzymes, primarily cytochrome P450 (CYP) isoenzymes, and membrane-bound transporters, including P-glycoprotein (P-gp) and organic anion-transporting polypeptides (OATPs) 11 , 12 .…”

Section: Introductionmentioning

confidence: 99%

“…Although statins are generally considered safe, their systemic exposure may be influenced by drug–drug interactions (DDI), which may increase the risk of statin-associated muscle symptoms (SAMS) 10 , 11 . These interactions are predominantly facilitated by metabolic enzymes, primarily cytochrome P450 (CYP) isoenzymes, and membrane-bound transporters, including P-glycoprotein (P-gp) and organic anion-transporting polypeptides (OATPs) 11 , 12 . However, the metabolism and transport of statins is far from well understood.…”

Section: Introductionmentioning

confidence: 99%

“…Numerous studies have confirmed the importance of OATP1B1 in the clinical efficacy and adverse reactions of statins, with a focus on SLCO1B1 SNPs 18 , 19 , 20 . In addition, due to the presence of SAMS and SNPs, more and more research has focused on statin-related DDI mediated by OATP1B1 10 , 11 , 12 . Therefore, it is critical to recognize the contribution of OATP1B1 to statin uptake to ensure their safe administration.…”

Section: Introductionmentioning

confidence: 99%

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Construction and characterization of a humanized SLCO1B1 rat model with its application in evaluating the uptake of different statins

Zhang,

Huang,

Huang

et al. 2024

Acta Pharmaceutica Sinica B

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Construction and characterization of a humanized SLCO1B1 rat model with its application in evaluating the uptake of different statins

Zhang,

Huang,

Huang

et al. 2024

Acta Pharmaceutica Sinica B

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“…Once ingested, several enzymes and transporters participate in its metabolism and transport in vivo. Until recently, drugmetabolizing enzymes, such as cytochrome P450 enzymes (CYPs), were considered the major determinants of statin disposition [3,[9][10][11]. Among these enzymes, those encoded by CYP3A4 and CYP3A5 are particularly important [12,13].…”

Section: Introductionmentioning

confidence: 99%

The Chinese-Han Population Carrying Wild-type Genotypes of SLCO1B1 388A>G, SLCO1B1 521T>C, CYP3A4 1B, CYP3A4 1G, and CYP3A5*3 Exhibits a Significant Alteration in the Pharmacokinetics of Atorvastatin Calcium

Xia,

Liu,

et al. 2023

J. Pharm. Res. Int.

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Due to the diverse genetic characteristics of metabolism and high drug plasma exposure, great inter-subject variability exists in the clinical efficacy and incidence of adverse events. This study aimed to evaluate the associations between the SLCO1B1 388A＞G (rs2306283) polymorphism and the pharmacokinetics of atorvastatin calcium (AC) in healthy volunteers who carried the wild genotypes of SLCO1B1 521T＞C (rs4149056), CYP3A4 1B (rs2740574), CYP3A4 1G (rs2242480), and CYP3A5*3 (rs776746). A FISH technique was employed to investigate the genetic polymorphisms in 187 healthy male volunteers. The pharmacokinetic study was conducted on a group of healthy male Chinese-Han volunteers with wild-type genotypes of SLCO1B1 521T>C, CYP3A4 1B, CYP3A41G and CYP3A53 genes, consisting of either mutant heterozygotes (n=10) or mutant homozygotes (n=10) of SLCO1B1 388A>G. The results were then compared to the pharmacokinetic parameters of AC in subjects with the wild-type genotype of SLCO1B1 388A>G, as previously described. Based on the distribution of genotypes, the 187 volunteers could be divided into 28 groups. The top 10 groups accounted for nearly 85% of the total volunteers. No significant differences (P>0.05) were observed in the pharmacokinetic parameters between subjects carrying homozygous and heterozygous genotypes of SLCO1B1 388A>G. However, The Cmax of subjects carrying the wild-type genotype of SLCO1B1 388A＞G was about 14.75 times higher than that of the heterozygous genotype group and 10.43 times higher than that of the homozygous genotype group. The AUC0-72h of volunteers with the wild-type genotype of SLCO1B1 388A＞G was about 13.81 times higher than that of the heterozygous genotype group and 11.96 times higher than that of the homozygous genotype group. Volunteers carrying wild genotypes of SLCO1B1 388A＞G, SLCO1B1 521T＞C, CYP3A4 1B, CYP3A4 1G, and CYP3A5*3 showed significantly higher levels of Cmax and AUC (P<0.01), as well as markedly decreased values of CLz/F and Vz/F (P<0.01) of AC. In conclusion, patients carrying the wild genotype of SLCO1B1 388A>G, SLCO1B1 521T>C, CYP3A41G, CYP3A41B, and CYP3A5*3 should receive a lower dose of AC to minimize the risk of adverse effects.

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Statin-induced myopathy: A rare entity?

Wirth,

Guis

2024

Joint Bone Spine

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Clinical conundrums involving statin drug-drug interactions

Cited by 4 publications

References 42 publications

Construction and characterization of a humanized SLCO1B1 rat model with its application in evaluating the uptake of different statins

Construction and characterization of a humanized SLCO1B1 rat model with its application in evaluating the uptake of different statins

The Chinese-Han Population Carrying Wild-type Genotypes of SLCO1B1 388A>G, SLCO1B1 521T>C, CYP3A4 1B, CYP3A4 1G, and CYP3A5*3 Exhibits a Significant Alteration in the Pharmacokinetics of Atorvastatin Calcium

Statin-induced myopathy: A rare entity?

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