Pharmacokinetic and safety interactions between aildenafil and clarithromycin, cimetidine, or rifampin in healthy subjects

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 ( C ₘₐₓ), area under the concentration‐time curve (AUC), time to reach C ₘₐₓ, and half‐life ( t 1/2 )—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 C max and 2.58 (2.42–2.76) for AUC 0−∞ . Conversely, rifampin markedly reduced aildenafil serum concentrations, with geometric mean ratios (90% CI) of 0.02 (0.02–0.03) for C max and 0.01 (0.01–0.02) for AUC 0−∞ . Coadministration with cimetidine resulted in log‐transformed C max and AUC 0−∞ 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 AUC 0−∞ by 2.58‐fold and C max 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.