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Antimicrobial Agents and Chemotherapy, October 2009, p. 4385-4392, Vol. 53, No. 10
0066-4804/09/$08.00+0     doi:10.1128/AAC.00449-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Differential Effects of Tipranavir plus Ritonavir on Atorvastatin or Rosuvastatin Pharmacokinetics in Healthy Volunteers{triangledown}

P. A. Pham,1* C. J. L. la Porte,2 L. S. Lee,1 R. van Heeswijk,2,{dagger} J. P. Sabo,3 M. M. Elgadi,4 P. J. Piliero,3 P. Barditch-Crovo,1 E. Fuchs,1 C. Flexner,1 and D. W. Cameron2

Johns Hopkins University School of Medicine, Baltimore, Maryland,1 University of Ottawa, The Ottawa Hospital and Ottawa Health Research Institute, Ottawa, Canada,2 Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut,3 Boehringer Ingelheim Canada, Ltd., Burlington, Ontario, Canada4

Received 3 April 2009/ Returned for modification 18 June 2009/ Accepted 3 August 2009

To identify pharmacokinetic (PK) drug-drug interactions between tipranavir-ritonavir (TPV/r) and rosuvastatin and atorvastatin, we conducted two prospective, open-label, single-arm, two-period studies. The geometric mean (GM) ratio was 1.37 (90% confidence interval [CI], 1.15 to 1.62) for the area under the concentration-time curve (AUC) for rosuvastatin and 2.23 (90% CI, 1.83 to 2.72) for the maximum concentration of drug in serum (Cmax) for rosuvastatin with TPV/r at steady state versus alone. The GM ratio was 9.36 (90% CI, 8.02 to 10.94) for the AUC of atorvastatin and 8.61 (90% CI, 7.25 to 10.21) for the Cmax of atorvastatin with TPV/r at steady state versus alone. Tipranavir PK parameters were not affected by single-dose rosuvastatin or atorvastatin. Mild gastrointestinal intolerance, headache, and mild reversible liver enzyme elevations (grade 1 and 2) were the most commonly reported adverse drug reactions. Based on these interactions, we recommend low initial doses of rosuvastatin (5 mg) and atorvastatin (10 mg), with careful clinical monitoring of rosuvastatin- or atorvastatin-related adverse events when combined with TPV/r.

* Corresponding author. Mailing Address: 1830 East Monument St., Rm. 444, Baltimore, MD 21287. Phone: (410) 502-4342. Fax: (410) 955-7889. E-mail: vpham{at}jhmi.edu

{triangledown} Published ahead of print on 10 August 2009.

{dagger} Present address: Tibotec BVBA, Mechelen, Belgium.

Antimicrobial Agents and Chemotherapy, October 2009, p. 4385-4392, Vol. 53, No. 10
0066-4804/09/$08.00+0     doi:10.1128/AAC.00449-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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