EFFECT OF N-3 POLYUNSATURATED FATTY-ACIDS ON CYCLOSPORINE PHARMACOKINETICS IN KIDNEY GRAFT RECIPIENTS - A RANDOMIZED PLACEBO-CONTROLLED STUDY

Highly concentrated marine polyunsaturated fatty acids (n-3 PUFA), aff ecting the lipids and lipophilic drugs metabolism, can interfere with cyclosporine (CyA) pharmacokinetics, This prospective, randomized and placebo-controlled, double-blind study involved 42 kidney graft recipi ents. From day +1, 21 pts (E) received 6 g n-3 PUFA (85% EPA + DHA, Es apent(R), Pharmacia) and 21 pts (P) received placebo (olive oil), both reduced to 3 g from day +30 on. A quadruple immunosuppressive regimen was employed. Plasma creatinine, lipids and CyA pharmacokinetics were investigated 1,3,6,9 and 12 months after graft, The two groups were c omparable for age, weight, M/F ratio, hypertension prevalence and base line lipids, Active treatment did not affect total and HDL-cholesterol , but significantly lowered triglycerides (E:120+/-12 vs P:166+/-21 mg /dl, p<0.0001), At one year, E pts had lower creatinine than P (1.26+/ -0.06 vs. 1.88+/-0.2 mg/dl, p<0.05), comparable CyA dosage, and a larg er CyA area under the curve (AUC) (n.s.), with a higher blood peak lev el (Cmax) (p<0.04) and less variance in time to peak (n.s.), The large r AUC in the E group at all intervals and the better pattern of plasma creatinine, with no rise in blood pressure, provided evidence of bett er CyA absorption and metabolism in n-3 PUFA supplemented kidney graft recipients.