Abstract：
:Ambrisentan is a nonsulfonamide, ET(A)-selective endothelin receptor antagonist (ERA) approved for the treatment of pulmonary arterial hypertension (PAH), and tadalafil is a phosphodiesterase type 5 (PDE-5) inhibitor under investigation for treatment of PAH. Due to the potential combination use, the pharmacokinetic (PK) interactions between these two drugs were assessed in a crossover study in 26 healthy adults. Single-dose PK of ambrisentan (10 mg) and its metabolite, 4-hydroxymethyl ambrisentan, were determined in the absence and presence of multiple doses of tadalafil (40 mg QD). Similarly, single-dose PK of tadalafil (40 mg) were evaluated in the absence and presence of multiple doses of ambrisentan (10 mg QD). In the presence of tadalafil, ambrisentan maximum plasma concentration (C(max)) was similar (105.0% [90% CI: 95.9-115.0%]) and systemic exposure (AUC(0-infinity)) was slightly decreased (87.5% [84.0-91.2%]), compared with ambrisentan alone. Similar changes were observed with 4-hydroxymethyl ambrisentan. Tadalafil C(max) (100.6% [94.4-107.1%]) and AUC(0-infinity) (100.2% [92.6-108.4%]) showed no difference in the absence and presence of ambrisentan. The safety profile of the drugs combined was similar to that of either drug alone. No dose adjustments should be necessary when these drugs are coadministered. These results are in contrast to previous reports that the sulfonamide-based ERA bosentan can cause marked decreases in the exposure of tadalafil.
journal_name
J Pharm Scijournal_title
Journal of pharmaceutical sciencesauthors
Spence R,Mandagere A,Harrison B,Dufton C,Boinpally Rdoi
10.1002/jps.21789subject
Has Abstractpub_date
2009-12-01 00:00:00pages
4962-74issue
12eissn
0022-3549issn
1520-6017pii
S0022-3549(16)33189-6journal_volume
98pub_type
杂志文章,随机对照试验abstract：:The reaction of UICEL-A/102, a cellulose II powder recently prepared from Avicel(R) PH-102 by treatment with an aqueous sodium hydroxide solution, with glutaraldehyde in 0.01 N HCl has been investigated to improve its binder properties, without adversely affecting the rapid disintegration characteristic. The results s...
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journal_title：Journal of pharmaceutical sciences
pub_type： 临床试验,杂志文章,随机对照试验
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