PHARMACODYNAMIC ACTIVITY OF LIPOPROTEIN-LIPASE AND HEPATIC LIPASE, AND PHARMACOKINETIC PARAMETERS MEASURED IN NORMOLIPIDEMIC SUBJECTS RECEIVING CIPROFIBRATE (100 OR 200 MG DAY) OR MICRONIZED FENOFIBRATE (200 MG/DAY) THERAPY FOR 23 DAYS/

The activities of lipoprotein lipase (LPL) and hepatic lipase (HL) wer e investigated after 23 days of ciprofibrate (100 mg or 200 mg) therap y or fenofibrate (200 mg) therapy. In a double-blind, double-placebo, cross-over study, three groups of six healthy volunteers received eith er 100 mg ciprofibrate/day followed by 200 mg fenofibrate 'high bioava ilability' (HB)/day, or vice versa (group A), 200 mg ciprofibrate/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 vers a (group C). Fasting plasma lipid levels and safety parameters were ev aluated before and after treatment. One hundred milligrams ciprofibrat e/day therapy was found to be approximately as effective as 200 mg fen ofibrate HB/day therapy in altering the lipid profile. The highest act ivation of LPL was obtained after treatment with 200 mg ciprofibrate/d ay. A modest, but statistically significant, increase in HL activity w as found after 100 or 200 mg ciprofibrate treatment. Investigation of the pharmacokinetics of ciprofibrate and fenofibric acid revealed a sh orter 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 cipro fibrate/day at increasing LPL and HL activity; however, 200 mg ciprofi brate/day is also associated with a potentially detrimental change in safety parameters. Two hundred milligrams fenofibrate HB/day therapy m ay represent an alternative therapy to 100 mg ciprofibrate/day for hyp erlipidaemic patients.