Send to

Choose Destination
Clin Pharmacol Ther. 1995 Oct;58(4):412-7.

In vivo inhibition profile of cytochrome P450TB (CYP2C9) by (+/-)-fluvastatin.

Author information

Division of Clinical Pharmacology, University Hospital, Geneva, Switzerland.



(+/-)-Fluvastatin is a synthetic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor that selectively and competitively inhibits P450TB (CYP2C9) in vitro. The potential for kinetic interactions in vivo between fluvastatin and P450TB substrates was therefore investigated in healthy volunteers.


Diclofenac (25 mg orally) oxidation was used as a marker of P450TB activity on days 0, 1, and 8 of fluvastatin treatment (40 mg/day).


Diclofenac peak concentration (Cmax) increased over time (0.28 [SD, 0.12], 0.38 [0.20], and 0.45 [0.4] mg/L on days 0, 1, and 8, respectively). Oral clearance was reduced on days 1 and 8 (14% and 15%, respectively). A time-dependent decrease in urinary metabolic ratio (MR, 4'-hydroxydiclofenac/diclofenac) was noted (1.07 [0.34], 0.90 [0.23] and 0.70 [0.18] on days 0, 1, and 8, respectively [p < 0.0001]) for the first 4 hours. The interaction was clear in only some individuals; MR reduction was related to baseline MR and it was more pronounced in subjects with a higher baseline MR (p < 0.01). Fluvastatin Cmax (0.18 [0.11] and 0.32 [0.1] mg/L on days 1 and 8, respectively) and area under the curve (0.28 [0.12] and 0.43 [0.15] on days 1 and 8, respectively; p < 0.001) increased over time. Diclofenac MR reduction was correlated with fluvastatin concentrations.


Interactions between fluvastatin and P450TB substrates (phenytoin, oral anticoagulants, oral hypoglycemic agents, and nonsteroidal antiinflammatory drugs) may occur, at least in some patients.

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center