title: Tacrolimus and cerivastatin pharmacokinetics and adverse effects after single and multiple dosing with cerivastatin in renal transplant recipients.
abstract: OBJECTIVE
  In contrast to cyclosporin, only limited information exists on the interaction potential between the immunosuppressive agent tacrolimus and HMG-CoA reductase inhibitors, which are metabolized via the cytochrome P450 system. The aim of this study was to investigate the pharmacokinetics, and adverse effects of cerivastatin combined with tacrolimus in renal transplant patients.
  
  
  METHODS
  Ten patients with stable kidney graft functions and LDL-cholesterol serum concentrations > 110 mg dl-1 were included in the study. After an observation period of 3 months, cerivastatin (0.2 mg daily) was administered for an additional 3 months. Tacrolimus steady-state pharmacokinetics and cerivastatin single- and multiple-dose pharmacokinetics were determined. Lipid concentrations, routine laboratory parameters and adverse events were obtained and analysed throughout the study period of 6 months.
  
  
  RESULTS
  Blood tacrolimus trough concentrations were not affected by cerivastatin (mean +/- SD 8.6 +/- 2.1 ng ml(-1) before, and 8.7 +/- 2.4 ng ml(-1) at day 90 of cerivastatin dosing, with a 95% confidence interval on the difference = 0.97, 1.08). The mean area under the blood concentration-time curve to 24 h (AUC(0,24 h)) for cerivastatin was 14.5 +/- 2.53 micro g l(-1) h(-1) at day 1 after starting treatment and 19.02 +/- 3.55 micro g l(-1) h(-1) (3 months later), resulting in a 35% higher (AUC(0,24 h)) compared with the first dose. Total cholesterol, LDL-cholesterol and triglyceride concentrations were significantly lowered by cerivastatin whereas no significant effect of cerivastatin on serum creatininkinase concentrations was observed and no adverse effects were documented.
  
  
  CONCLUSIONS
  Tacrolimus increased the AUC(0, 24 h) of cerivastatin by a mean of 35% in renal transplant patients. Cerivastatin had no detectable effect on the pharmacokinetics of tacrolimus.
authors.affiliation: University Hospital of Schleswig-Holstein, Campus Kiel, Division of Nephrology, 24105 Kiel, Germany. renders@nephro.uni-kiel.de
authors.forename: Lutz
authors.initials: L
authors.lastname: Renders
authors.forename: Christian S
authors.initials: CS
authors.lastname: Haas
authors.forename: Jan
authors.initials: J
authors.lastname: Liebelt
authors.forename: Martin
authors.initials: M
authors.lastname: Oberbarnscheidt
authors.forename: Harald O
authors.initials: HO
authors.lastname: Schöcklmann
authors.forename: Ulrich
authors.initials: U
authors.lastname: Kunzendorf
mesh_terms: D000328:Adult; D000368:Aged; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004338:Drug Combinations; D004347:Drug Interactions; D005260:Female; D006207:Half-Life; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D016559:Tacrolimus / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D004338:Drug Combinations; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007166:Immunosuppressive Agents; D011725:Pyridines; C086276:cerivastatin; D016559:Tacrolimus