Anemia and Immunosuppressive Regimen in Renal Transplanted Patients: Single-Center Retrospective Study.

We compared retrospectively the level of hemoglobin and the percentage of patients with anemia among 59 kidney transplant recipients receiving everolimus, cyclosporine, and corticosteroids and 128 treated with cyclosporine, mycophenolic acid, and corticosteroids. We also compared age at the time of transplantation, sex and ferritine, serum creatinine, creatinine clearance, folic acid, cyanocobalamine levels, use od recombinant erythropoietin, mean corpuscolar volume at the last ambulatory control. Statistical analysis included Student t test, χ(2) test, and logistic regression. The analysis was performed using SPSS software. We observed no difference in terms of hemoglobin levels in patients treated with everolimus (12.9 ± 1.6 vs 12.7 ± 1.5 g/dL). Anemia (defined as hemoglobin <13 g/dL in men and <12 g/dL in women, or need to use erythropoietin) was found in 49% and 45% of patients in the 2 groups respectively (P = .6). The other parameters evaluated were similar except for the mean corpuscular volume, which was significantly lower in the everolimus group. In the multivariate analysis only serum creatinine and estimated glomerular filtration rate influenced the level of hemoglobin. We observed no differences in terms of development of anemia in renal transplanted patients treated with everolimus-based regimen.

5 year comparison of very low-dose cyclosporine and high-dose everolimus vs standard cyclosporine and enteric-coated mycophenolate in renal transplantation patients.

In this retrospective study, we compared the outcome of renal transplanted patients who received everolimus (EVR) (C0: 8-12 ng/mL)+cyclosporine (CsA) (C2: 150-300 ng/mL)+steroids, vs those who received enteric-coated mycophenolate sodium (EC-MPS) (1,440 mg/d)+CsA (C2: 500-700 ng/mL)+steroids. Efficacy was evaluated at 5 years. We found a nonsignificant trend toward a better 5-year graft survival (81.2% vs 68.6%) and better graft function (estimated glomerular filtration rate 71.8±35.7 vs 60.0±26.2 mL/min, P=.114) in favor of the EVR group. In our experience, EVR with a very low dose of CsA was associated with a nonstatistical trend toward better renal function and graft survival compared to a standard regimen of CsA and EC-MPS.

Discovery of CP-199,330 and CP-199,331: two potent and orally efficacious cysteinyl LT1 receptor antagonists devoid of liver toxicity.

CP-199,330 (3) and CP-199,331 (4) are cysLT1 receptor antagonists that are equipotent to marketed cysLT1 receptor antagonists zafirlukast and pranlukast, show good pharmacokinetics in rats and monkeys, and are devoid of liver toxicity in monkeys as seen in CP-85,958 (1).

Development of new chromanol antagonists of leukotriene D4.

By addressing the issues of potency and metabolism in 3, a new series of LTD4 antagonists represented by (+)-26 was developed which is equipotent to clinical LTD4 antagonists Zafirlukast (1) and Pranlukast (2).

N-carbamoyl analogs of Zafirlukast: potent receptor antagonists of leukotriene D4.

Exploration of the indole nitrogen region of Zafirlukast (1) has uncovered a potent series of cysteinyl leukotriene D4 (LTD4) antagonists. These studies showed that a variety of functionality could be incorporated in this region of the molecule without sacrificing potency. Efforts to exploit this site in order to improve oral efficacy are discussed.

Development of 2,2-dimethylchromanol cysteinyl LT1 receptor antagonists.

A new series of cysLT1 receptor antagonists represented by CP-288,886 (7) and CP-265,298 (8) were developed which are equipotent to clinical cysLT1 receptor antagonists Zafirlukast (1) and Pranlukast (2).