The impact of (1:1) cyclosporine A conversion to its microemulsion formulation on the kidney function of patients with cardiac allografts.
Due to the large variations in the absorption and bioavailability of conventional cyclosporine A (CyA), 1:1 (mg:mg) conversion to its microemulsion formulation (Neoral) has been advocated in transplant recipients. However, the renal hazards and biochemical effects of such conversions and not known in cardiac transplant recipients. In this study, 68 cardiac transplant recipients who were receiving conventional CyA, for a period of 61.3 +/- 36.0 (mean +/- standard error (SE)) months, were switched to the microemulsion formulation (Neoral). The biochemical and renal function tests were evaluated at 1, 3, 6, 9 and 12 months pre- and post-conversion of CyA. The results obtained post-conversion were compared with those of the baseline (pre-conversion). Serum creatinine and uric acid levels significantly increased post-conversion to the microemulsion formulation. One patient required discontinuation of the microemulsion in an attempt to reverse severe renal failure. In spite of a significant decrease in the microemulsion dose at 6, 9 and 12 months, there was a significant increase in the whole blood CyA trough levels at 9 and 12 months of conversion. There was no significant change in blood pressure, serum total cholesterol or potassium post-conversion. Our results suggest that after 1:1 (mg:mg) conversion of CyA to its microemulsion formulation, there will be a significant rise in serum creatinine, uric acid and whole blood trough CyA levels necessitating significant dose reduction. This effect is probably due to the markedly improved absorption and bioavailability of the latter.
Khajehdehi
P
P
Division of Nephrology, St. Louis University School of Medicine 63110, USA.
Yip
D
D
Bastani
B
B
D000042:Absorption; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001682:Biological Availability; D001794:Blood Pressure / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D002784:Cholesterol / Q000097:blood; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D004655:Emulsions; D005260:Female; D005500:Follow-Up Studies; D016027:Heart Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011188:Potassium / Q000097:blood; D051437:Renal Insufficiency / Q000139:chemically induced; D014527:Uric Acid / Q000097:blood
D004655:Emulsions; D007166:Immunosuppressive Agents; D014527:Uric Acid; D016572:Cyclosporine; D002784:Cholesterol; D003404:Creatinine; D011188:Potassium