Drug interactions of the statins and consequences for drug selection

The role of common variants of ABCB1, CYP3A4, and CYP3A5 genes in lipid-lowering efficacy and safety of simvastatin treatment

“…No significant associations were observed between the CYP3A4 −392A>G and CYP3A5 6986A>G allele variants and the efficacy of simvastatin (data not shown). Because CYP3A4 expression is known to be affected by many coadministered drugs that are CYP3A4 substrates, inhibitors, or inducers, 24 , 25 data for association of −392A>G polymorphism were reanalyzed excluding patients taking CYP3A4 substrates, inhibitors, or inducers. Again, no association was disclosed between CYP3A4 gene polymorphism and changes in lipid and lipoprotein levels after treatment in this subsample (data not shown).…”

Iatrogenic and toxic myopathies

“…The HMG‐CoA reductase inhibitors can induce rhabdomyolysis, particularly in patients with concomitant use of gemfibrozil,121 cyclosporine,2 diltiazem,75 erythromycin,5 itraconazole,90 or nicotinic acid,126 or in patients with severe hepatobiliary dysfunction and renal insufficiency 151. In such instances, increased myotoxicity is attributed to interference with the hepatic cytochrome P450 3A4 enzyme causing a marked increase in HMG‐CoA reductase inhibitory activity 14. The concomitant use of HMG‐CoA reductase inhibitors with gemfibrozil or cyclosporine carries a high risk of rhabdomyolysis.…”

Absorption Barriers in the Rat Intestinal Mucosa: 1. Application of an In Situ Perfusion Model to Simultaneously Assess Drug Permeation and Metabolism

“…In total, the absorptive flux of a drug molecule across the intestinal mucosa is a complex process influenced by the factors described above and can be simply defined as: This equation illustrates that the absorptive flux ( J ) of a molecule is a function of the surface area of the intestine ( A ), the drug‐concentration gradient across the intestinal mucosa ( C ), and the effective permeability of the drug‐molecule itself (Pe) 3, 20. By definition, any change in absorptive flux, assuming the intestinal area and concentration gradients remain constant, must be accompanied by a change in drug permeability (Pe) as demonstrated in cases of drug–food21–23 and, drug–drug24–26 interactions. Numerous in vitro models such as isolated jejunal mucosa27, 28 and cultured intestinal epithelial cells29 have been employed to investigate the underlying mechanisms and modulating events of intestinal drug absorption; however, each has limitations that may restrict the in vivo relevance of the resulting data.…”