Effect of atorvastatin and fluvastatin on the metabolism of midazolam by cytochrome P450 in vitro.
basic_science · Level V
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Abstract
We have investigated the effects of the statins atorvastatin and fluvastatin on the cytochrome P450 3A4 enzyme (CYP 3A4)-mediated metabolism of midazolam in vitro, using pooled human liver microsomes. Midazolam was metabolised by human hepatic microsomes with a Michaelis-Menten constant (K(m)) of 5.25 (SD 1.2) micromol.l(-1). Atorvastatin was a moderate competitive inhibitor of CYP 3A4 with an inhibitory constant (K(i)) of 12.4 (95% CI 4.65-20.06) micromol.l(-1). Fluvastatin was a weak non-competitive inhibitor of CYP 3A4 with a K(i) of 94.3 (95% CI 55.01-133.5) micromol.l(-1). Both atorvastatin and fluvastatin inhibit the CYP 3A4-mediated metabolism of midazolam in vitro.
Medical subject headings
- Cytochrome P-450 Enzyme Inhibitors
- Fatty Acids, Monounsaturated
- Heptanoic Acids
- Hydroxymethylglutaryl-CoA Reductase Inhibitors
- Indoles
- Midazolam
- Pyrroles