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Updated: Apr 28, 2026

High-throughput Identification of Synergistic Drug Combinations by the Overlap2 Method
Published on: May 21, 2018
A Drug-Drug Interaction of Ainuovirine with Fluconazole in Healthy Adults and Dose Optimization Informed by
Jianfei Huang1,2, Yan Lei3, Weiping Cai1,2
1Infectious Disease Center, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, People's Republic of China.
Purpose:
The study aimed to assess the drug-drug interaction (DDI) and safety of ainuovirine (a new-generation non-nucleoside reverse transcriptase inhibitor, primarily metabolized by CYP2C19) coadministered with fluconazole, a strong CYP2C19 inhibitor, in healthy adults.
Methods:
This was a multiple-dose, open-label, two-period, parallel, sequential study. In group A, 18 participants received ainuovirine (150 mg, q.d.) from day 1-7 (Period 1), followed by coadministration with fluconazole (200 mg, q.d.) from day 8-14 (Period 2). In group B, 18 participants received fluconazole (200 mg, q.d.) from day 1-7 (Period 1), followed by coadministration with ainuovirine (150 mg, q.d.) from day 8-14 (Period 2). A physiologically based pharmacokinetic (PBPK) model of ainuovirine predicted its DDI with fluconazole, incorporating population PK analysis.
Results:
In group A, when coadministered with fluconazole, geometric means of ainuovirine C max,ss, AUC0-24,ss increased up to 233.0% and 349.6%, respectively, versus ainuovirine alone. In group B, there were no apparent effects of ainuovirine on C max,ss, AUC0-24,ss and T max,ss for fluconazole. No death or grade ≥3 serious adverse events occurred. The predictive performance of the PBPK model for the interaction scenario is excellent, because the ratios of predicted-to-observed Cmax,ss and AUC0-∞,ss are very close to 1.0, which provides high confidence in the model's simulations for dose optimization.
Conclusion:
Coadministration with fluconazole significantly alters the steady-state PK of ainuovirine, but not conversely. The DDI PBPK model supports that dose reduction of ainuovirine is warranted for coadministration with fluconazole.
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