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Tacrolimus and cerivastatin pharmacokinetics and adverse effects after single and multiple dosing with cerivastatin in renal transplant recipients
Author(s) -
Renders Lutz,
Haas Christian S.,
Liebelt Jan,
Oberbarnscheidt Martin,
Schöcklmann Harald O.,
Kunzendorf Ulrich
Publication year - 2003
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1046/j.1365-2125.2003.01870.x
Subject(s) - cerivastatin , pharmacokinetics , tacrolimus , pharmacology , adverse effect , urology , dosing , drug interaction , atorvastatin , medicine , chemistry , cholesterol , transplantation , pravastatin
Aims 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 µg l −1 h −1 at day 1 after starting treatment and 19.02 ± 3.55 µg 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.