Sildenafil is a selective inhibitor of cGMP-specific type 5 phosphodiesterase used for the treatment of pulmonary arterial hypertension (PAH) in the adults. In pediatrics, PAH treatment options include the off-label use of sildenafil. Sildenafil is metabolized in the liver by cytocrome P450 into its active metabolite, N-desmethyl sildenafil. The determination of plasma levels of sildenafil and N-desmethyl sildenafil could be useful for therapy optimization and pharmacokinetic studies. We have developed and validated a method for the quantification of sildenafil and its metabolite in plasma of children by rapid extraction, using high-performance liquid chromatography with ultraviolet detection. The calibration range was fitted at least square model (r ≥ 0.999), with an accuracy and an intra- and inter-day relative standard deviation <15% for both analytes. The mean recovery was 102.5% for sildenafil and 101.8% for N-desmethyl sildenafil. This simple method could be successfully used in children with PAH under treatment with sildenafil.
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http://dx.doi.org/10.1002/bmc.3765 | DOI Listing |
J Pharm Biomed Anal
October 2024
Doping Control Laboratory, Department of Pharmacology, Istanbul Pendik Veterinary Control Institute, Istanbul 34890, Turkiye.
The use of prohibited substances in horse racing is a major concern that jeopardizes both the fairness of competitions and the health of horses. This problem can stem from the use of licensed drugs for animal health, as well as unlicensed substances. Horse doping laboratories monitor the potential use of these substances in racehorses within the framework of regulations set by the International Federation of Horse Racing Authority.
View Article and Find Full Text PDFFront Pharmacol
March 2023
Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.
Sildenafil is a potent vasodilator and phosphodiesterase type five inhibitor, commercially known as Revatio and approved for the treatment of pulmonary arterial hypertension. Maternal administration of sildenafil during pregnancy is being evaluated for antenatal treatment of several conditions, including the prevention of pulmonary hypertension in fetuses with congenital diaphragmatic hernia. However, determination of a safe and effective maternal dose to achieve adequate fetal exposure to sildenafil remains challenging, as pregnancy almost always is an exclusion criterion in clinical studies.
View Article and Find Full Text PDFPharmaceuticals (Basel)
October 2022
Research Center for High Altitude Medicine, Qinghai University Medical College, Xining 810000, China.
(1) Background: High-altitude hypoxia has been shown to affect the pharmacokinetic properties of drugs. Although there is a high incidence of cardiovascular disease among individuals living in high-altitude areas, studies on the effect of high-altitude hypoxia on the pharmacokinetic properties of cardiovascular drugs are limited. (2) Methods: The aim of this study was to evaluate the pharmacokinetics of nifedipine, bosentan, simvastatin, sildenafil, and their respective main metabolites, dehydronifedipine, hydroxybosentan, simvastatin hydroxy acid, and N-desmethyl sildenafil, in rats exposed to high-altitude hypoxia.
View Article and Find Full Text PDFSci Rep
May 2022
Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea.
Sildenafil is widely used off-label in pediatric patients with pulmonary arterial hypertension (PAH). This study was conducted to characterize the pharmacokinetics (PK) of sildenafil in term and preterm neonates with PAH, by developing a population PK model, and to suggest appropriate doses to achieve clinically effective concentrations. A population PK modelling analysis was performed using sildenafil and its metabolite N-desmethyl sildenafil (DMS) concentration data from 19 neonates with PAH, whose gestational ages ranged 24-41 weeks.
View Article and Find Full Text PDFJ Chromatogr Sci
September 2021
BE/Phase I Clinical Center, The First Affiliated Hospital of Xiamen University, No. 55, Zhenhai Road, Xiamen, China.
A sensitive high-performance liquid chromatography-tandem mass spectrometry method was established for the simultaneous determination of sildenafil and N-desmethyl sildenafil in human plasma. The protein precipitation was used for extraction and the gradient elution of the mobile phase A of water (containing 0.01% formic acid) and the mobile phase B of acetonitrile, and methanol (V:V = 1:1, containing 0.
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