Time-of-intake (morning versus evening) of extended-release fluvastatin in hyperlipemic patients is without influence on the pharmacodynamics (mevalonic acid excretion) and pharmacokinetics.
OBJECTIVE
Statins inhibit the rate-limiting step in cholesterol biosynthesis, the conversion of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) to mevalonate by HMG-CoA reductase. Statins are usually taken in the evening as the HMG-CoA reductase activity is high during the night. This recommendation might not apply if statins are given as extended-release (ER) formulations. The present study investigated the influence of time of intake of fluvastatin 80 mg ER on cholesterol biosynthesis. Main objectives were to measure the change in 24-hour urinary mevalonic acid excretion, to determine plasma concentrations of mevalonic acid and fluvastatin and to monitor triglycerides, total cholesterol, HDL-cholesterol and LDL-cholesterol.


METHODS
This was a randomized, 2-period crossover study in 26 hypercholesterolemic patients who received a single daily dose of fluvastatin both in the morning and in the evening.


RESULTS
At baseline, the amount of mevalonic acid was 204.9 +/- 68.1 microg/g creatinine. After a single dose of fluvastatin mean urine values of mevalonate were significantly reduced to 129.8 +/- 66.2 micro/g (evening) and to 118.7 +/-34.3 microg/g (morning; n.s. between groups), thus representing a reduction of about 39%. Compared to baseline, plasma mevalonate concentrations were decreased by fluvastatin resulting in similar 24-hour profiles after the morning and the evening dosage. The pharmacokinetics of fluvastatin were similar in both periods of the study, with higher plasma concentrations for several hours following the evening dosage.


CONCLUSIONS
This study demonstrates that fluvastatin ER is equally effective in inhibiting cholesterol biosynthesis when given once daily in the morning and once daily in the evening.
Fauler
G
G
Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University Graz, Austria. guenter.fauler@meduni-graz.at
Abletshauser
C
C
Erwa
W
W
Löser
R
R
Witschital
K
K
März
W
W
D000328:Adult; D015415:Biomarkers; D002784:Cholesterol / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D005229:Fatty Acids, Monounsaturated / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D000077340:Fluvastatin; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006949:Hyperlipidemias / Q000097:blood / Q000188:drug therapy* / Q000652:urine; D007211:Indoles / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D008798:Mevalonic Acid / Q000097:blood / Q000652:urine*; D008875:Middle Aged; D013997:Time Factors; D014280:Triglycerides / Q000097:blood
D015415:Biomarkers; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D003692:Delayed-Action Preparations; D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D014280:Triglycerides; D000077340:Fluvastatin; D002784:Cholesterol; D008798:Mevalonic Acid