Time‐Dependent Interaction Between Lopinavir/Ritonavir and Fexofenadine

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Abstract
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.