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Author: Admin | 2025-04-28
Drugs to be excreted to the lowest level of quantification before the next period. Moreover, the AUCτ,ss/AUCinf,ss of both tadalafil and amlodipine were over 80% (data not shown). Blood sampling was performed for up to 72 h after the last dosing to estimate the exposures of tadalafil and amlodipine sufficiently.Recently, Kim et al reported that the Cmax and Tmax of amlodipine were 18.4 ng/mL and 6.0 h in subjects administered 10 mg amlodipine for 10 d, respectively.12 Their results are consistent with the results presented in this study (19.6 ng/mL and 5.95 h). The AUC of tadalafil increased proportionally with dose in healthy subjects administered 2.5 to 20 mg of tadalafil. Steady-state plasma concentrations were attained within 5 d of administering the drug once per day, and exposure was approximately 1.6-fold greater after a single dose, similar to the profile in this study.In this study, the primary PK parameters were Cmax,ss and AUCτ,ss of tadalafil and amlodipine. The administration of tadalafil alone increased both Cmax,ss and AUCτ,ss significantly compared with the co-administration of tadalafil and amlodipine; 90% CIs for the GMRs of Cmax,ss and AUCτ,ss were all out of the range of 0.80–1.25. However, the 90% CIs for the GMRs of combined administration versus monotherapy of amlodipine were within the range of 0.80–1.25 for Cmax,ss and AUCτ,ss.Tadalafil is predominantly metabolized by CYP3A4, and CCBs such as amlodipine, diltiazem, and verapamil are known to be a potent CYP3A4 inhibitor.8,9 These facts could explain why the Cmax,ss and AUCτ,ss of tadalafil were remarkably increased in the group of tadalafil plus amlodipine in the present study. Although the plasma level of tadalafil concentration in co-administration treatment was greater than monotherapy treatment, and the frequency of AEs such as a remarked decrease in blood pressure was not significantly different. Sildenafil, other PDE-5 inhibitor, and antihypertensive dihydropyridines such as amlodipine were metabolized by CYP3A4. However, administration of sildenafil and amlodipine did not exhibit a synergistic blood pressure-lowering action.13,14The most common AE was headache in the treatment group of tadalafil alone and tadalafil with amlodipine, which was a well-known AE of tadalafil. As shown in Table 2 and Figure 2, tadalafil was absorbed rapidly (Tmax,ss= 2.61 h) and decreased to the approximate baseline by 24 h after dosing. Likewise, the AE, which started at least 3 h late after drug administration, was almost resolved within 2 d.The limitation of the present study is that the subjects
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