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Antimicrobial Agents and Chemotherapy, September 2002, p. 3091-3093, Vol. 46, No. 9
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.9.3091-3093.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Voriconazole Inhibition of the Metabolism of Tacrolimus in a Liver Transplant Recipient and in Human Liver Microsomes

Raman Venkataramanan, Shimin Zang, Timothy Gayowski, and Nina Singh*

School of Pharmacy, University of Pittsburgh, and Veterans Affairs Medical Center, Pittsburgh, Pennsylvania

Received 14 December 2001/ Returned for modification 28 April 2002/ Accepted 18 June 2002

The purpose of this study was to assess the effect of voriconazole on the blood tacrolimus concentration in a liver transplant recipient and to examine the interaction between voriconazole and tacrolimus by using human liver microsomes. Two subjects were enrolled in the clinical study: one received voriconazole, and the other received a placebo. Tacrolimus metabolism was evaluated in human liver microsomes at various concentrations in the absence and presence of various concentrations of voriconazole. Coadministration of voriconazole and tacrolimus resulted in elevated (nearly 10-fold-higher) trough tacrolimus blood concentrations in the liver transplant patient. In the in vitro study, voriconazole at a concentration of 10.4 ± 4.3 µg/ml inhibited the metabolism of tacrolimus by 50%. Clinically relevant concentrations of voriconazole inhibited the metabolism of tacrolimus in human liver microsomes. Close monitoring of the blood concentration and adjustment in the dose of tacrolimus are warranted in transplant recipients treated with voriconazole.

* Corresponding author. Mailing address: VA Medical Center, Infectious Disease Section, University Drive C, Pittsburgh, PA 15240. Phone: (412) 688-6179. Fax: (412) 688-6950. E-mail: nis5+{at}pitt.edu.

Antimicrobial Agents and Chemotherapy, September 2002, p. 3091-3093, Vol. 46, No. 9
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.9.3091-3093.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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