A logistic-regression model provides novel guidelines to maximize the anti-acute rejection properties of cyclosporine with a minimum of toxicity.
Although cyclosporine has become the mainstay of immunosuppression in organ transplantation, there is still no consensus on the criteria to optimize its anti-rejection activity with minimum toxicity. A clear and objective definition of target cyclosporine trough levels at different times from renal transplantation is still lacking, primarily because of the lack of a model correlating cyclosporine levels with probability of rejection or toxicity. In this study, logistic-regression model was developed that was applied to data collected retrospectively from two postoperative periods, i.e., Days 0 to 9 and 10 to 30, in 135 consecutive cadaveric renal transplant recipients, for a total of 1851 determinations. Only minimum and maximum trough levels were considered for each period. Concentration-response curves were estimated for Days 0 to 9 (P = 0.0001 for efficacy and P = 0.028 for toxicity) and for Days 10 to 30 (P = 0.015 for efficacy and P = 0.037 for toxicity). Therapeutic intervals of 330 to 430 ng/mL (parent compound in whole blood) for Days 0 to 9 and 260 to 390 ng/mL for Days 10 to 30 predicted an incidence of acute rejection of 22% and 12%, respectively, with a reasonably low toxicity that primarily consisted of elevation of serum aminotransferases.
Perna
A
A
Mario Negri Institute for Pharmacological Research, Bergamo, Italy.
Gotti
E
E
de Bernardis
E
E
Perico
N
N
Remuzzi
G
G
D000328:Adult; D016572:Cyclosporine / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D007674:Kidney Diseases / Q000139:chemically induced / Q000517:prevention & control* / Q000601:surgery; D016030:Kidney Transplantation / Q000276:immunology*; D016015:Logistic Models; D008875:Middle Aged; D008954:Models, Biological; D011446:Prospective Studies
D007166:Immunosuppressive Agents; D016572:Cyclosporine