Interaction between several medicines and statins

Arzneimittelforschung. 2003;53(3):145-53. doi: 10.1055/s-0031-1297087.

Abstract

To gain a better understanding of drug-drug interaction between various medicinal substances and statins, in vitro experiments using human hepatic microsomes were performed. The metabolic clearance of atorvastatin (CAS 134523-00-5) was about 32 microliters/min/mg protein, some 15-fold greater than that of pitavastatin (CAS 147526-32-7). On co-incubation with several medicinal substances, metabolic inhibition of pitavastatin was negligible in human hepatic microsomes. However, a remarkable metabolic inhibition of atorvastatin was noted in the presence of various medicinal substances. The intrinsic clearance of atorvastatin lactone was 20-fold greater than that of its acid form, whereas no marked difference was noted between pitavastatin and its lactone form. Pitavastatin lactone showed no inhibitory effect on CYP3A4-mediated metabolism of testosterone in contrast to atorvastatin lactone. These results suggest that pitavastatin and its lactone form will be highly unlikely to interact with other drugs in clinical practice.

MeSH terms

  • Acids / metabolism
  • Anticholesteremic Agents / adverse effects*
  • Anticholesteremic Agents / pharmacokinetics
  • Atorvastatin
  • Chromatography, High Pressure Liquid
  • Cytochrome P-450 CYP2D6 / metabolism
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 Enzyme System / metabolism
  • Drug Interactions
  • Heptanoic Acids / adverse effects*
  • Heptanoic Acids / pharmacokinetics
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacokinetics
  • In Vitro Techniques
  • Indicators and Reagents
  • Lactones / metabolism
  • Microsomes, Liver / metabolism
  • Pyrroles / adverse effects*
  • Pyrroles / pharmacokinetics
  • Quinolines / adverse effects*
  • Quinolines / pharmacokinetics

Substances

  • Acids
  • Anticholesteremic Agents
  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Indicators and Reagents
  • Lactones
  • Pyrroles
  • Quinolines
  • Cytochrome P-450 Enzyme System
  • Atorvastatin
  • CYP3A protein, human
  • Cytochrome P-450 CYP2D6
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human
  • pitavastatin