Background: The effectiveness of sildenafil in the management of pulmonary hypertension in congenital diaphragmatic hernia (CDH) has been reported but has not been systematically evaluated. Our studies have also demonstrated that intra-amniotic (IA) sildenafil administration improves pulmonary hypertension in CDH.
Methods: We evaluated the pharmacokinetics of sildenafil after IA administration in pregnant rabbits. Following maternal laparotomy, fetuses received IA injection of 0.8 mg of sildenafil. Maternal blood, amniotic fluid, and fetal tissues were collected at various time points. The concentrations of sildenafil and its major metabolite in samples were analyzed by liquid chromatography-mass spectrometry. To assess organ toxicity, 7 days after IA sildenafil administration, fetal organs were examined histologically.
Results: After IA dosing, sildenafil was absorbed quickly with an absorption half-life of 0.03-0.07 h into the fetal organs. All the organs showed a maximum concentration within 1 h and the disposition half-life ranged from 0.56 to 0.73 h. Most of the sildenafil was eliminated from both mothers and fetuses within 24 h after a single dose. There was no histological evidence of organ toxicity in the fetuses after a single dose of IA administration of sildenafil.
Conclusion: IA sildenafil is rapidly absorbed into the fetus, distributes into the mother, and is eliminated by the mother without accumulation or fetal organ toxicity. This study confirms the feasibility and the safety of IA administration of sildenafil and enables future applications in the treatment of CDH fetuses.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.taap.2023.116527 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Contribution of the community pharmacist workforce to primary care through the lens of medicines classification: comparison of Aotearoa New Zealand and Australia.
J Prim Health Care
December 2024
Curtin Medical School, Faculty of Health Sciences, Curtin University, Perth, WA 6102, Australia.
Introduction Optimal use of the workforce in primary care is critical due to increasing complexity and demand resulting from multi-morbidity in ageing populations. Improving public access to medicines by making them available via a pharmacist without prescription can support self-care while ensuring oversight by a health professional. Aim The aim of this paper was to identify and explore key differences between New Zealand and Australia in medicines classified nationally for pharmacist-only non-prescription supply.
View Article and Find Full Text PDF[Effect of Zhishi Xiebai Guizhi Decoction on phenotypic transformation of pulmonary artery smooth muscle cells in rats with hypoxic pulmonary hypertension].
Zhongguo Zhong Yao Za Zhi
October 2024
Qinghai University Xining 810001, China Research Center for High Altitude Medicine, Medical College, Qinghai University Xining 810001, China.
This study aims to investigate the effect of Zhishi Xiebai Guizhi Decoction on the phenotypic transformation of pulmonary artery smooth muscle cells(PASMCs) in rats with hypoxic pulmonary hypertension(HPH). Healthy SPF SD rats were randomly assigned to five groups: control group, hypoxia model group, hypoxia + low-dose Zhishi Xiebai Guizhi Decoction group(440 mg·kg~(-1)·d~(-1)), hypoxia + high-dose Zhishi Xiebai Guizhi Decoction group(880 mg·kg~(-1)·d~(-1)), and hypoxia + sildenafil group(30 mg·kg~(-1)·d~(-1)), with right rats in each group. Rats in the hypoxia model and hypoxia + drug groups were exposed to a hypobaric oxygen chamber with a simulated altitude of 5 000 m to induce the PH model.
View Article and Find Full Text PDFEvaluation of the effect of daily tadalafil 5 mg versus daily sildenafil 25 mg on neutrophil-lymphocyte and platelet-lymphocyte ratios in patients with erectile dysfunction: A comparative randomized controlled study.
Arch Ital Urol Androl
October 2024
Department of Andrology & STDs, Faculty of Medicine, Assiut University.
Background: Previous studies had shown that the neutrophils/lymphocytes (NLR) and platelets/lymphocytes (PLR) ratios could be used as markers of inflammatory load as well as prognostic factors in several medical conditions. The current study aimed to compare the effect of using daily tadalafil 5 mg/day versus daily sildenafil 25 mg/day in improving erectile function as well as their ability to reduce NLR and PLR.
Methods: One hundred and four participants were recruited.
Discovery and Optimization of Dihydroquinolin-2(1)-ones as Novel Highly Selective and Orally Bioavailable Phosphodiesterase 5 Inhibitors for the Treatment of Pulmonary Arterial Hypertension.
J Med Chem
December 2024
Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Science, Southern Medical University, Guangzhou 510515, P. R. China.
Article Synopsis
- A newly optimized compound showed potent inhibition of PDE5A with an impressive selectivity over other PDE enzymes, indicating strong potential as a treatment option.
- In animal studies, the compound outperformed sildenafil in reducing mean pulmonary artery pressure and right ventricle hypertrophy, suggesting it could be a promising new therapy for PAH.
Purpose Of The Study: Comparison of the pharmacokinetic characteristics of the drug Vildegra registered in the Russian Federation with literature data for the original drug Viagra.
Materials And Methods: Study design: prospective, open-label in healthy volunteers with a single oral dose on an empty stomach. The study included 48 male volunteers aged 18 to 45 years with a verified diagnosis of "healthy.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!