Journal Article

Pharmacokinetics of atorvastatin and its metabolites after single and multiple dosing in hypercholesterolaemic haemodialysis patients

Robert L. Lins, Katelijne E. Matthys, Gert A. Verpooten, Patrick C. Peeters, Max Dratwa, Jean‐Claude Stolear and Norbert H. Lameire

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 18, issue 5, pages 967-976
Published in print May 2003 | ISSN: 0931-0509
Published online May 2003 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfg048
Pharmacokinetics of atorvastatin and its metabolites after single and multiple dosing in hypercholesterolaemic haemodialysis patients

Show Summary Details

Preview

Background. Patients with chronic renal failure commonly suffer from a secondary form of complex dyslipidaemia, and may benefit from lipid‐lowering treatment. Atorvastatin has been shown to reduce efficiently the levels of atherogenic lipoproteins also in patients with renal failure, but pharmacokinetic data in haemodialysis patients are lacking.

Methods. In this study, hypercholesterolaemic haemodialysis patients received 40 mg (n=12) or 80 mg (n=11) atorvastatin once daily, first as a single dose and then continuously for 2 weeks. Plasma levels of atorvastatin and its active and inactive metabolites were measured by LC/MS/MS, and pharmacokinetic parameters (Cmax, tmax, AUC, t1/2) compared between single and multiple dosing, and between the different doses.

Results. The pharmacokinetic parameters of the parent drug atorvastatin acid were not significantly different after single and 2‐week multiple dosing; they showed dose‐proportionality between the 40 and 80 mg dose, and were comparable to findings in healthy volunteers. Dose‐proportionality and absence of accumulation was also observed for the major active metabolite ortho‐hydroxy‐atorvastatin and the inactive metabolites atorvastatin lactone and ortho‐hydroxy‐atorvastatin lactone, but the levels of the active metabolite were relatively lower, and the inactive metabolites higher, compared with healthy volunteers. The para‐hydroxy‐metabolites constituted only a minor pathway in atorvastatin's metabolic elimination. Haemodialysis did not cause enhanced clearance of atorvastatin or its metabolites, the drug was well tolerated and there were no serious adverse events.

Conclusion. While subtle differences may exist in the metabolic processing of atorvastatin in haemodialysis patients, active drug did not accumulate nor did it show enhanced elimination, and levels were comparable to those measured in healthy volunteers. Therefore there is no need to adapt atorvastatin dosage in this particular patient population.

Keywords: atorvastatin; haemodialysis; metabolites; pharmacokinetics; renal insufficiency; safety

Journal Article.  6114 words.  Illustrated.

Subjects: Nephrology

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.