tadalafil, Cialis
Analysis of undeclared synthetic phosphodiesterase-5 inhibitors in dietary supplements and herbal matrices by LC-ESI-MS and LC-UV.

Gratz SR, Flurer CL, Wolnik KA.

US Food and Drug Administration, Forensic Chemistry Center, Cincinnati, OH 45237-3097, USA. sgratz ora.fda.gov

A liquid chromatography-electrospray ionisation-mass spectrometry (LC-ESI-MS) method was developed to screen for the presence of synthetic phosphodiesterase type 5 (PDE-5) inhibitors including sildenafil, tadalafil and vardenafil. The method was applied to the analysis of dietary supplements and bulk herbal materials. Bulk powders or composites of tablets, capsules or liquids were prepared and an extraction of PDE-5 inhibitors was performed using a mixture of acetonitrile and water with sonication. Identification of sildenafil, vardenafil or tadalafil was accomplished using a single quadrupole mass spectrometer coupled to a liquid chromatograph with an electrospray interface. Positive ion detection in the full scan mode was used while in-source collision induced dissociation (CID) provided several structurally significant fragment ions to aid in the mass spectral identification. Approximately half of the 40 botanical products analyzed were found to contain undeclared synthetic PDE-5 inhibitors. For products found to contain one of these three compounds by LC-MS, HPLC with UV detection was used for quantitation.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15522526&dopt=Abstract tadalafil Cialis



tadalafil, Cialis
Development of a Micellar electrokinetic capillary chromatography method for the determination of three drugs employed in the erectile dysfunction therapy.

Rodriguez Flores J, Berzas Nevado JJ, Castaneda Penalvo G, Mora Diez N.

Department of Analytical Chemistry and Foods Technology, UCLM 13071, Ciudad Real, Spain. juana.rflores uclm.es

A Micellar electrokinetic capillary chromatography method is proposed for the determination of sildenafil, vardenafil and tadalafil, which are employed in oral therapy for erectile dysfunction. Optimum conditions for the separation were investigated. A background electrolyte solution consisting of 10 mM phosphate buffer adjusted to pH 12.0, sodium dodecyl sulfate (SDS) 25 mM, hydrodynamic injection, and 25 kV as separation voltage were used. Relative standard deviations (R.S.D.s) were 1.0, 1.0, 0.4% and 2.9, 2.9, 1.9% for migration time and corrected peak area (CPA) (n = 9) for sildenafil, vardenafil and tadalafil, respectively. Detection limits obtained for the three drugs ranged from 0.19 to 0.61 mg L(-1). A linear concentration range between 1 and 20 mg L(-1) was obtained. A ruggedness test of this method was checked using the fractional factorial model of Plackett-Burman, in which the influence of six factors at three different levels was tested on different electrophoretic results: resolution and corrected peak area. The statistical evaluation of the electrophoretic results was achieved by Youden and Steiner method. The described method is rapid, sensitive and rugged and it was tested in the pharmaceutical formulations analysis obtaining recoveries between 98 and 107% respect to the nominal content.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15522725&dopt=Abstract tadalafil Cialis



tadalafil, Cialis
High biochemical selectivity of tadalafil, sildenafil and vardenafil for human phosphodiesterase 5A1 (PDE5) over PDE11A4 suggests the absence of PDE11A4 cross-reaction in patients.

Weeks JL, Zoraghi R, Beasley A, Sekhar KR, Francis SH, Corbin JD.

1Department of Molecular Physiology and Biophysics, Vanderbilt University, School of Medicine, Nashville, Tennessee, USA.

The physiological role of phosphodiesterase (PDE)11 is unknown and its biochemical characteristics are poorly understood. We have expressed human His-tagged PDE11A4 and purified the enzyme to apparent homogeneity. PDE11A4 displays K(m) values of 0.97 muM for cGMP and 2.4 muM for cAMP, and maximal velocities were 4- to 10-fold higher for cAMP than for cGMP. Given the homology between PDE11 and PDE5, we have compared the biochemical potencies of tadalafil (Cialistrade mark, Lilly-ICOS), vardenafil (Levitratrade mark, Bayer-GSK), and sildenafil (Viagratrade mark, Pfizer Inc.) for PDE11A4 and PDE5A1. PDE5A1/PDE11A4 selectivities are 40-, 9300-, and 1000-fold for tadalafil, vardenafil, and sildenafil, respectively. This suggests that none of these three compounds is likely to crossreact with PDE11A4 in patients.International Journal of Impotence Research (2005) 17, 5-9. doi:10.1038/sj.ijir.3901283 Published online 11 November 2004.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15538396&dopt=Abstract tadalafil Cialis



tadalafil, Cialis
[Viagra, sialis, impase--which of them, to whom, when and how?]

[Article in Russian]

[No authors listed]

The study has been performed of the efficacy in the treatment of erectile dysfunction (ED) of oral drugs affecting nitric oxide: impase and phosphodiesterase-5 (PDE-5) inhibitors--sildenafil citrate (viagra), tadalafil (sialis)--alone and in combination with impase. A total of 218 ED patients aged 21-73 years (mean age 58.1 +/- 13.2 years) were divided into 3 groups comparable by the number of the patients, age, suspected etiology, pathogenesis and ED severity. Group 1 (n = 81) took viagra in the individually adjusted dose for 6 months; group 2 (n = 64) received sialis in a dose 20 mg for 6 months; group 3 (n = 73) took impase 1 tablet each other day sublingually for 6 months. Overall efficacy made up 77.8, 81.3 and 56.2% for viagra, sialis and impase, respectively. In view of different mechanism of action of PDE-5 inhibitors (viagra, sialis) and impase we combined the drugs in those who failed monotherapy or had drastic side effects. The combination raised efficacy of pharmacotherapy from 56.2 to 92.2%. We came to the conclusion that in psychogenic, isolated neurogenic, compensated and subcompensated arteriogenic ED of a mild or moderate degree, the treatment can be started with impase. If it was uneffective, in severe ED or moderate venoocclusive ED it is better to use PDE-5 inhibitors (viagra, sialis). If one of the latter fails, the other should be administered. If the inhibitors have low efficacy or in side effects, it is indicated to use their combination with impase.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15560162&dopt=Abstract tadalafil Cialis



tadalafil, Cialis
Impact of diabetes mellitus on the severity of erectile dysfunction and response to treatment: analysis of data from tadalafil clinical trials.

Fonseca V, Seftel A, Denne J, Fredlund P.

Section of Endocrinology and Metabolism, Tulane University Health Sciences Centre, 1430 Tulane Avenue-SL 53, New Orleans, LA 70112, USA. vfonseca tulane.edu

AIMS/HYPOTHESIS: A retrospective analysis of pooled data from twelve placebo-controlled trials was conducted to characterise the efficacy and safety of tadalafil for the treatment of erectile dysfunction in men with diabetes compared with that in men without diabetes. METHODS: Patients were randomly allocated to tadalafil 10 mg, 20 mg, or placebo, taken as needed for 12 weeks. The study population comprised 637 men with diabetes (mean age 57 years) and 1681 men without diabetes (mean age 56 years). RESULTS: At baseline, patients with diabetes had more severe erectile dysfunction than patients without diabetes, with mean International Index of Erectile Function (IIEF) erectile function domain scores of 12.6 and 15.0 respectively (p<0.001). Compared with placebo, tadalafil 10 mg and 20 mg improved all primary efficacy outcomes in both patient groups (p<0.001). Men with diabetes receiving tadalafil 20 mg experienced a mean improvement of 7.4 in their IIEF erectile function domain score against baseline versus 0.9 for placebo (p<0.001). This group reported on average that 53% of their attempts at intercourse were successful, compared with 22% for placebo (p<0.001 for the change from baseline). Baseline IIEF erectile function domain scores correlated inversely with baseline HbA(1)c levels. The responses to tadalafil were similar regardless of levels of baseline glycaemic control, diabetic therapy received, or previous use of sildenafil. CONCLUSIONS/INTERPRETATION: Despite more severe baseline erectile dysfunction in men with diabetes, tadalafil was efficacious and well tolerated in this population. As reported for other phosphodiesterase 5 inhibitors, the response to tadalafil was slightly lower in men with diabetes than in men without diabetes.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15599697&dopt=Abstract tadalafil Cialis