Pharmacodynamic activity of lipoprotein lipase and hepatic lipase, and pharmacokinetic parameters measured in normolipidaemic subjects receiving ciprofibrate (100 or 200 mg/day) or micronised fenofibrate (200 mg/day) therapy for 23 days.
The activities of lipoprotein lipase (LPL) and hepatic lipase (HL) were investigated after 23 days of ciprofibrate (100 mg or 200 mg) therapy or fenofibrate (200 mg) therapy. In a double-blind, double-placebo, cross-over study, three groups of six healthy volunteers received either 100 mg ciprofibrate/day followed by 200 mg fenofibrate 'high bioavailability' (HB)/day, or vice versa (group A), 200 mg ciprofibrate HB/day followed by 200 mg fenofibrate HB/day, or vice versa (group B), or 100 mg ciprofibrate/day followed by 200 mg ciprofibrate/day, or vice versa (group C). Fasting plasma lipid levels and safety parameters were evaluated before and after treatment. One hundred milligrams ciprofibrate/day therapy was found to be approximately as effective as 200 mg fenofibrate HB/day therapy in altering the lipid profile. The highest activation of LPL was obtained after treatment with 200 mg ciprofibrate/day. A modest, but statistically significant, increase in HL activity was found after 100 or 200 mg ciprofibrate treatment. Investigation of the pharmacokinetics of ciprofibrate and fenofibric acid revealed a shorter time to reach peak plasma levels, but a longer elimination half life for the ciprofibrate preparations in comparison with fenofibrate. A dose of 200 mg ciprofibrate/day is more effective than 100 mg ciprofibrate/day at increasing LPL and HL activity; however, 200 mg ciprofibrate/day is also associated with a potential detrimental change in safety parameters. Two hundred milligrams fenofibrate HB/day therapy may represent an alternative therapy to 100 mg ciprofibrate/day for hyperlipidaemic patients.
Desager
J P
JP
Pharmacotherapy Laboratory, Catholic University of Louvain, Brussels, Belgium.
Horsmans
Y
Y
Vandenplas
C
C
Harvengt
C
C
D000328:Adult; D002851:Chromatography, High Pressure Liquid; D002995:Clofibric Acid / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D011345:Fenofibrate / Q000493:pharmacokinetics / Q000494:pharmacology; D058607:Fibric Acids; D006207:Half-Life; D006801:Humans; D000960:Hypolipidemic Agents / Q000493:pharmacokinetics* / Q000494:pharmacology*; D008049:Lipase / Q000097:blood*; D008071:Lipoprotein Lipase / Q000097:blood*; D008099:Liver / Q000201:enzymology*; D008297:Male; D009391:Nephelometry and Turbidimetry; D012016:Reference Values
D058607:Fibric Acids; D000960:Hypolipidemic Agents; D002995:Clofibric Acid; D008049:Lipase; D008071:Lipoprotein Lipase; C019304:ciprofibrate; D011345:Fenofibrate