E Stragliotto — Page 2

PubMed1985

Differential effects of aspirin and indomethacin on platelet and leukocyte thromboxane A2 formation.

In this study, the in vitro inhibitory effects of aspirin and indomethacin on the arachidonic acid induced thromboxane B2 formation by human leukocytes, are evaluated. The results are compared to those obtained using similarly challenged human washed platelets. Acetylsalicylic acid inhibition, calculated as IC50 by a dose-response curve, is more than ten fold higher for leukocytes vs platelets. In fact, a concentration of aspirin as low as 5 microM almost completely suppresses thromboxane B2 formation by washed platelets, whereas a concentration of 50 microM is necessary to achieve the same inhibition with leukocytes. Indomethacin (0.001-100 microM), incubated with platelet and leukocyte suspensions acts similarly to aspirin. Leukocyte and platelet cyclooxygenases are, therefore, differently affected by both aspirin and indomethacin. These differences may be relevant in the understanding of the wide divergence between the aspirin doses used in thrombosis prevention and in the treatment of inflammatory disease.

Aspirin↗

PubMedDate not supplied

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), affecting 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 recipients. From day +1, 21 pts (E) received 6 g n-3 PUFA (85% EPA + DHA, Esapent, 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 comparable for age, weight, M/F ratio, hypertension prevalence and baseline 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 larger CyA area under the curve (AUC) (n.s.), with a higher blood peak level (Cmax) (p < 0.04) and less variance in time to peak (n.s.). The larger AUC in the E group at all intervals and the better pattern of plasma creatinine, with no rise in blood pressure, provided evidence of better CyA absorption and metabolism in n-3 PUFA supplemented kidney graft recipients.

Adult↗