Comparative study of once and 3-times daily regimens of bezafibrate in patients with primary hyperlipoproteinaemia

Summary

A single-blind crossover trial was carried out to compare the effects of treatment with bezafibrate, 400 mg once daily or 200 mg 3-times daily, in 26 patients with primary hyperlipoproteinaemia. The patients were treated for 8 weeks with one regimen followed by an untreated period of 7 weeks before crossing over to the second regimen. All lipid fractions measured (total cholesterol, triglycerides, LDL, VLDL and HDL cholesterol) showed closely corresponding changes during treatment. During the first 4-weeks' treatment with the 3-times daily regimen, total cholesterol levels were reduced in virtually all patients (96%), the mean level showing a highly significant (p<0.001) decrease of 76.7 mg/ 100 ml, i.e. from 356.3 to 279.6 mg/100 ml. During the second 4-weeks' treatment, total cholesterol levels showed some degree of increase in the majority of patients (76%), the mean level increasing significantly (p<0.05) by 12.0 mg/ 100 ml, i.e. from 279.6 to 291.6 mg/ 100 ml. Over the full 8-week treatment period, the reduction (from 356.3 to 291.6 mg/100 ml) was highly significant (p<0.001). Similar results were obtained with the once daily regimen. During the first 4-weeks' treatment, total cholesterol levels were reduced in virtually all patients (90%), the mean level showing a highly significant (p<0.001) decrease of 51.9 mg/100 ml, i.e. from 338.8 to 286.9 mg/ 100 ml. During the second 4-weeks' treatment, total cholesterol levels showed some degree of increase in the majority of patients (69%), the mean level increasing significantly (p<0.01) by 17.8 mg/100 ml, i. e. from 286.9 to 304.7 mg/100 ml. Over the full 8-week treatment period, the reduction (from 338.8 to 304.7 mg/100 ml) was highly significant (p<0.001). The reduction in lipid levels was somewhat greater, although not significantly so, with the 3-times daily regimen but this must be interpreted in the light of the larger total daily dose (600 mg as compared with 400 mg). Over the 8-week treatment period slightly more patients (14 patients -54%) showed greater reductions with the once daily regimen as compared with 3-times daily. In practical terms, this suggests that the two regimens were similar in their effect on lipids. The 'secondary increase' in total cholesterol seen between the fourth and eighth weeks of treatment occurred most markedly in the period after crossover. Possible reasons for this are discussed. Mean levels of triglyceride, LDL and VLDL levels behaved similarly to total cholesterol, although in the case of trigly cerides and VLDL the mixture of' both Type IIa and Type IIb hyperlipo-proteinaemia resulted in a large scatter of individual results. HDL cholesterol showed the expected converse changes and, surprisingly, no tendency for the 'secondary increase'. Alkaline phosphatase levels showed sustained highly significant decreases throughout treatment with both dosage regimens, confirming the good patient compliance. Other liver function tests, electrolytes, protein levels and white blood count showed no clinically relevant changes during bezafibrate therap. There were small, but statistically significant, progressive increases in urea and creatinine. Both dosage regimens of bezafibrate were well tolerated and no patient experienced any symptoms which could definitely be related to drug therapy. The results indicate that 400 mg bezafibrate once daily is well tolerated and has similar effects on serum lipids as does a regimen of 200 mg 3-times daily over a treatment period of 8 weeks.

Key Words::

• Bezafibrate
• antilipaemic agents
• hyperlipoproteinaemia