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Time-Dependent Interaction Between Lopinavir/Ritonavir and Fexofenadine

From the Ottawa Hospital, Division of Infectious Diseases (Dr van Heeswijk, Ms Seguin, Dr Cameron) and Department of Pharmacy (Dr van Heeswijk); The Ottawa Health Research Institute (Dr van Heeswijk, Mr Bourbeau, Ms Campbell, Dr Cameron); Ottawa Genome Center (Ms Campbell); University of Ottawa (Mr Chauhan, Dr Foster, Dr Cameron), Ottawa, Ontario, Canada.

This study investigated the effect of single-dose and steady-state lopinavir/ritonavir on the exposure to fexofenadine, as a measure of P-glycoprotein activity. Sixteen volunteers (8 women) received single-dose oral fexofenadine 120 mg alone, in combination with single-dose ritonavir 100 mg or lopinavir/ritonavir 400/100 mg (randomized 1:1, stratified by sex), and in combination with steady-state lopinavir/ritonavir 400/100 mg twice daily. Single-dose ritonavir and lopinavir/ritonavir increased the area under the fexofenadine plasma concentration-time curve from 0 to infinity (AUC) by 2.2- and 4.0-fold, respectively (P < .02). Steady-state lopinavir/ritonavir increased the fexofenadine AUC by 2.9-fold. No changes were observed in the fexofenadine elimination half-life (P > .12). The fexofenadine AUC was increased by lopinavir/ritonavir, likely due to increased bioavailability secondary to P-glycoprotein inhibition. After repeated administration of lopinavir/ritonavir, the interaction was attenuated compared to the single-dose effect, although a net inhibitory effect was maintained. Time-dependent inhibition of P-glycoprotein by lopinavir/ritonavir should be considered when P-glycoprotein substrates are coadministered.

Key Words: HIV • protease inhibitors • P-glycoprotein • lopinavir • fexofenadine

Address for reprints: Rolf P. G. van Heeswijk, PharmD, PhD, Tibotec BVBA, Gen De Wittelaan L11B3, 2800 Mechelen, Belgium; e-mail: rvheesw1{at}tibbe.jnj.com.

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