ArticleFrontiers in physiology2022
Changes in CYP3A4 Enzyme Expression and Biochemical Markers Under Acute Hypoxia Affect the Pharmacokinetics of Sildenafil.
Article in Frontiers in physiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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5 citing papers in PubMed, 9 citations in OpenAlex.
- Regulatory mechanism of ABCB1 transcriptional repression by HDAC5 in rat hepatocytes under hypoxic environment.Frontiers in physiology · 2025Article
- Progress in Epigenetic Modification Regulating Drug Transporters in the Hypoxic Environment.Current drug delivery · 2025Review
- Effects of plateau hypoxia on population pharmacokinetics and pharmacodynamics of metformin in patients with Type 2 diabetes.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2023Article
- Editorial: Drug metabolism and transport: the Frontier of personalized medicine.Frontiers in pharmacology · 2023Article
- The mechanism of colon tissue damage mediated by HIF-1α/NF-κB/STAT1 in high-altitude environment.Frontiers in physiology · 2022Article
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2 authors at 1 institution in 1 country.
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Abstract
To investigate the effects of pathological, physiological, biochemical and metabolic enzymes CYP3A4 on the pharmacokinetics of sildenafil under acute hypoxia, rats were randomly divided into the plain group (50 m above sea level), acute plateau group 1 (2300 m above sea level), and acute plateau group 2 (4300 m above sea level), and blood samples and liver tissues were collected. Our results showed that the blood gas, physiological and biochemical indexes of rats changed under acute hypoxia, and the protein expression of CYP3A4 enzyme decreased. The process of absorption, distribution, metabolism and excretion of sildenafil in rats has changed. Compared with the P group, the area under the drug-time curve and the average resident in the H2 group increased to 213.32 and 72.34%, respectively. The half-life and peak concentration increased by 44.27 and 133.67%, respectively. The clearance rate and apparent distribution volume decreased to 69.13 and 46.75%, respectively. There were no statistical differences in the pharmacokinetic parameters between the P group and the H1 group. In conclusion, the pharmacokinetic changes of sildenafil have a multi-factor regulation mechanism, and changes in blood gas, pathology, and biochemical indicators and metabolic enzymes affect the absorption, distribution, excretion, and metabolism of sildenafil, respectively. This study provides experimental evidence and new ideas for the rational use of sildenafil under acute hypoxic conditions.
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