British journal of clinical pharmacology · 2026
Pharmacokinetic and safety interactions between aildenafil and clarithromycin, cimetidine, or rifampin in healthy subjects.
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Xie Ran, Zhao Nan, Jia Bo, Cheng Lu, Xu Junyu, Wang Xia, Zhao Xia, Cui Yimin
Аннотация
AIMS: Aildenafil citrate, an orally bioavailable phosphodiesterase type 5 (PDE5) inhibitor, is primarily metabolized by cytochrome P450 3A4 (CYP3A4). This study aimed to assess potential pharmacokinetic interactions between aildenafil citrate tablets and cytochrome P450 (CYP)3A modulators.
METHODS: This study involved three open-label, fixed-sequence trials in healthy subjects. Participants received a single oral dose of aildenafil 60 mg alone and with repeated doses of clarithromycin (500 mg, CYP3A4 inhibitor, N = 18), rifampin (600 mg, inducer, N = 18), or cimetidine (400 mg, N = 18). Pharmacokinetic (PK) parameters-including maximum serum concentration (Cₘₐₓ), area under the concentration-time curve (AUC), time to reach Cₘₐₓ, and half-life (t1/2)-were calculated using noncompartmental analysis from serial serum aildenafil concentrations. Adverse events were monitored throughout.
RESULTS: Clarithromycin significantly increased aildenafil exposure, with geometric mean ratios (90% CI) of 1.67 (1.51-1.85) for Cmax and 2.58 (2.42-2.76) for AUC0-∞. Conversely, rifampin markedly reduced aildenafil serum concentrations, with geometric mean ratios (90% CI) of 0.02 (0.02-0.03) for Cmax and 0.01 (0.01-0.02) for AUC0-∞. Coadministration with cimetidine resulted in log-transformed Cmax and AUC0-∞ ratios near 1.0 (0.99 and 1.17, respectively), with geometric mean ratios (90% CI) of 0.99 (0.84-1.16) and 1.17 (1.10-1.25), indicating no significant effect on aildenafil exposure.
CONCLUSIONS: Coadministration of aildenafil with the strong CYP3A4 inhibitor clarithromycin increased aildenafil AUC0-∞ by 2.58-fold and Cmax by 1.67-fold; therefore, dose adjustment should be guided by clinical response and tolerability. In contrast, coadministration with the strong CYP3A4 inducer rifampin is not recommended.
METHODS: This study involved three open-label, fixed-sequence trials in healthy subjects. Participants received a single oral dose of aildenafil 60 mg alone and with repeated doses of clarithromycin (500 mg, CYP3A4 inhibitor, N = 18), rifampin (600 mg, inducer, N = 18), or cimetidine (400 mg, N = 18). Pharmacokinetic (PK) parameters-including maximum serum concentration (Cₘₐₓ), area under the concentration-time curve (AUC), time to reach Cₘₐₓ, and half-life (t1/2)-were calculated using noncompartmental analysis from serial serum aildenafil concentrations. Adverse events were monitored throughout.
RESULTS: Clarithromycin significantly increased aildenafil exposure, with geometric mean ratios (90% CI) of 1.67 (1.51-1.85) for Cmax and 2.58 (2.42-2.76) for AUC0-∞. Conversely, rifampin markedly reduced aildenafil serum concentrations, with geometric mean ratios (90% CI) of 0.02 (0.02-0.03) for Cmax and 0.01 (0.01-0.02) for AUC0-∞. Coadministration with cimetidine resulted in log-transformed Cmax and AUC0-∞ ratios near 1.0 (0.99 and 1.17, respectively), with geometric mean ratios (90% CI) of 0.99 (0.84-1.16) and 1.17 (1.10-1.25), indicating no significant effect on aildenafil exposure.
CONCLUSIONS: Coadministration of aildenafil with the strong CYP3A4 inhibitor clarithromycin increased aildenafil AUC0-∞ by 2.58-fold and Cmax by 1.67-fold; therefore, dose adjustment should be guided by clinical response and tolerability. In contrast, coadministration with the strong CYP3A4 inducer rifampin is not recommended.