An open label, balanced, randomized, two-treatment, two-sequence, two-period, crossover, single-dose bioequivalence study was conducted in healthy adult male subjects, under fasting conditions. Twelve healthy subjects were enrolled in a single-centre, randomized, single-dose, open-label, 2-way crossover study, with a minimum washout period of 7 days.
Plasma samples were collected up to The pharmacokinetics parameter for the reference R and test T for sildenafil was as follow: Elimination rate constant Kel for these products were calculated as 0. For piperazine n-desmethyl sildenafilthe pharmacokinetics parameter for the reference R and test T was as follow: All Published work is licensed under a Creative Commons Attribution 4. NIL Source of Support: It acts by inhibitingc GMP - specific phosphodiesterase type 5, an enzyme that promotes degradation of cGMP, which regulates the blood flow in the penis.
The chemical structure of Sildenafil is shown in fig. Sildenafil, when used properly, is relatively safe. There are, however, certain side effects that could create potential hazards.
Sildenafil has been shown to potentiate the hypotensive effects of nitrates commonly employed in the treatment of certain heart conditions . Moreover, while sildenafil inhibitsPDE5, it also has a high affinity for phosphodiesterase type 6 PDE6 , which is a retinal enzyme involved in photo transduction [3, 4]. Most of the reported methods show that extraction of sildenafil and its main metabolites are made using solid phase extraction .
Many analytical methods, using high performance liquid chromatography HPLC , have been published for quantification of the parent drug sildenafil in plasma and not for its active metabolite, using ultraviolet visible UV—Vis detector [12, 13]. Most of the methods were developed for estimation of sildenafil alone from pharmaceuticals[16, 17]. Many physicians consider sildenafil a good first-line therapy for erectile dysfunction and an alternative to the use of oral androgens, injection of intracavemosal or transurethral prostaglandins, or vacuum devices.
After oral administration, sildenafil is rapidly absorbed, reaching peak plasma concentrations in min . In the present study, we have reported a highly sensitive, selective and reproducible analytical method for the determination of sildenafil, and its metabolite piperazine n-desmethyl sildenafil inplasma samples utilizing liquid chromatography coupled to electrospray ES tandem mass spectrometry by using liquid—liquid extraction methods.
Clarithromycin was used as an internal standard. We have developed and validated the method as per the FDA guidelines over a concentration range of 1. The retention times of sildenafil, piperazine n-desmethyl sildenafil and clarithromycin were0.
The method validated as per FDA guidelines and was employed in the analysis of plasma samplesafter oral administration of sildenafil tablets mg in healthy human volunteers [22, 23]. Water was purified by Direct-Q water purification system from Millipore. Formic acid was of analytical grade and were obtained also from Merck. Sildenafil citrate and piperazine n-desmethylsildenafil were provided by Pfizer. Clarithromycin is used as an internal standard.
Analytical columns Thermo Hypersil Gold Column 50x2. The pump was used under isocratic conditions on manual mode and detector was operated at nm. Sonication was done for the mobile phase prior to usage. The separation was under isocratic conditions with a flow rate of 0. The mass spectrometric parameters were optimized to obtain maximum sensitivity at unit resolution.
Preparation of Calibration Standards and Quality Control Samples A stock solution of sildenafil, piperazine ndesmethyl sildenafil were prepared in methanol at a concentration of 1. Standard solutions for sildenafil 5. Low, medium, and high concentration quality control for sildenafil QC solutions The stock solution of IS 1. Preparation of Samples Sample preparation consisted of the addition of 0.
Analysis of Patient Samples The bioanalytical method developed previously was applied to quantify sildenafil and piperazine n-desmethyl sildenafil concentrations in plasma following oral administration of healthy human volunteers. These volunteers were contracted in Vertex Laboratory Research Ltd. Each one of the 12 healthy volunteers were administered a mg dose one mg tablet orally with ml of drinking water.
The product Viagra tablets R Pfizer mg and the test viagra tablets T formulation were used. Blood samples were collected aspre-dose 0 hr 5 min prior to dosing followed by further samples at 0. After dosing, 4 ml blood sample was collected each time in vaccutainers containing CPDA.
Test and reference were administered to the same human volunteers under fasting conditions separately with proper washing periods as perprotocol. Pharmacokinetics and Statistical Analysis Pharmacokinetics parameters from human plasma samples were calculated by using Win- Non-Lin 5. Plasma sildenafil, piperazine n-desmethyl sildenafil concentration-time profiles were visually inspected and Cmax and Tmax values were determined. The AUC0—t was obtained by trapezoidal method.
The terminal elimination rate constant Ke , was estimated from the slope of the terminal exponential phase of the plasma of sildenafil, piperazine n-desmethyl sildenafil concentration-time curve by means of the linear regression method. The goal of this work is to quantify the drug sildenafil and its metabolite piperazine n-desmethyl sildenafil in human plasma. Chromatographic conditions, especially the composition and nature of the mobile phase were optimized through several trials to achieve best resolution and increase the signal of analytes and internal standard.
Plasma concentrations versus time profiles are shown in Fig. All the plasma concentrations of sildenafil and piperazine n-desmethyl sildenafil were in the standard curve region and retained above LLOQ for the entire sampling period. The observed values were reported inTable 4 and Table 5 for sildenafil and for piperazine n-desmethyl sildenafil. Therefore, it can be concluded that the two analyzed formulations reference and test are bioequivalent. The methoddescribed here is accurate, robust and fast.
Each sample requiresless than 1 min run time. The sensitivity of the assay is sufficient to followaccurately the pharmacokinetics of sildenafil and piperazine n-desmethylsildenafil following oral administration.
Conflict of Interests The authors declare that there is no conflict of interests regarding the publication of this paper. Phosphodiesteraseinhibitors for erectile dysfunction in patients with diabetes mellitus. Ralph D, McNicholas T.
UK management guidelines for erectile dysfunction. Sildenafil and nonnitrateantihypertensive medications. N Engl J Med. Blank, J Anal Toxico! Determination of sildenafil citrate and its main metabolite bysample stacking with polarity switching using micellarelectrokineticchromatography. Liquid chromatographic tandem mass spectrometry method for the quantitation of sildenafil in human plasma.
Quantitative analysis of sildenafil and demethylsildenafil in human serum by liquid chromatography-mass spectrometry with minimal sample pretreatment. Langtry HD, Markham A. A review of its use in erectile dysfunction. Yritia, Arzneimittelforschung, , 58 3 , Xu and Se Pu, Chinese, , 23 6 , —5.
Guidance for industry bioanalytical method validation, U. Guidance for industry Food- effect bio availability and Fed Bioequivalence studies. Select your language of interest to view the total content in your interested language. Can't read the image? Related article at Pubmed , Scholar Google.
Sildenafil citrate, 1-[4-ethoxy 6,7-dihydro methyloxopropyl-1H-pyrazolo[4,3-d]pyrimidin- 5-yl phenylsulfonyl]-4methylpiperazine, is primarily indicated in the treatment oferectile dysfunction . Methanol and Acetonitrile were obtained from S. The chromatographic separation was performed on Thermo Hypersil Gold Column 50x2. A stock solution of sildenafil, piperazine ndesmethyl sildenafil were prepared in methanol at a concentration of 1.
Sample preparation consisted of the addition of 0. The bioanalytical method developed previously was applied to quantify sildenafil and piperazine n-desmethyl sildenafil concentrations in plasma following oral administration of healthy human volunteers.
Pharmacokinetics parameters from human plasma samples were calculated by using Win- Non-Lin 5. The validated method was used in the determination of sildenafil and piperazine ndesmethyl sildenafil in plasma samples for establishing the pharmacokinetics parameters of a single mg dose one mg tablet in 12 healthy volunteers.
The authors declare that there is no conflict of interests regarding the publication of this paper.
To determine the absolute bioavailability, dose proportionality and the effects of food on the pharmacokinetics of single oral doses of sildenafil citrate. Br J Clin Pharmacol. ;53 Suppl SS. Pharmacokinetics of sildenafil after single oral doses in healthy male subjects: absolute bioavailability, food. Pharmacokinetics and Metabolism. VIAGRA is rapidly absorbed after oral administration, with absolute bioavailability of about. 40%. Its pharmacokinetics are.
Pharmacokinetics Of Sildenafil is a highly rated Canadian Pharmacy online which delivers low-priced generic and branded prescription drugs directly to your door. Generic and . No effect on sildenafil pharmacokinetics 1. No change in efficacy of sildenafil for treatment of ED 1. Antifungals, azole (itraconazole, ketoconazole) Possible increased systemic exposure of sildenafil 1 Consider lower initial sildenafil dose (25 mg) for treatment of ED 1 Concomitant use not recommended in patients receiving. We provide full service adult Sildenafil Pharmacokinetics in a meticulously clean environment with state-of-the-art equipment. Dr. Dr. Sharp and his staff strive to provide consistently exceptional results whether your treatment requires implants, complicated bridgework, treatment for gum disease, dentures or simply routine restorations.
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