Tadalafil selectivity

Sildenafil (Viagra ), tadalafil (Cialis ), and vardenafil (Levitra ) act by selectively inhibiting phosphodiesterase (PDE) type 5, an enzyme that breaks down cGMP. By inhibiting the breakdown of cGMP, smooth muscle relaxation is... 

Selective ala-blockers (such as 0.4 mg tamsulosin every day) are appropriate in combination with tadalafil. 

Pharmacology Sildenafil, tadalafil, and vardenafil are selective inhibitors of... 

Ketoconazole (400 mg daily), a selective and potent inhibitor of CYP3A4, increased tadalafil 20-mg single-dose exposure (AUC) by 312%. Other CYP inhibitors—Although specific interactions have not been studied, other CYP3A4 inhibitors, such as erythromycin, itraconazole, and grapefruit juice, would likely increase tadalafil exposure. 

Tadalafil has also been extensively evaluated in patients with cardiovascular disease and has a similar safety and efficacy profile to sildenafil (45). Studies have shown no adverse effects on cardiac contraction, ventricular repolarization, or ischemic threshold. A similar hypotensive effect has been recorded with a dose of doxazosin 8 mg so caution is needed. As hypotension does not occur in the supine position and as tadalafil has a long half-life it is suggested that tadalafil is taken in the morning and doxazosin in the evening. There is no interaction of tadalafil with the selective a-adrenoceptor antagonist tamsulosin, which can, therefore, be prescribed as an alternative to doxazosin for symptomatic benign prostate hypertrophy (46). 

These drugs enhance the effect of nitric oxide by inhibiting phosphodiesterase type 5. Tadalafil has cross-reactivity with phosphodiesterase type 11, which may cause back pain and myalgia. The approximately 4000-fold selectivity for phosphodiesterase type 5 versus type 3 is important because type 3 is involved in the control of cardiac contractility. 

Tadalafil (Cialis ) [4—11], which is a cyclic guanosine monophosphate (cGMP) specific T)rpe V phosphodiesterase (PDE5) inhibitor similar to sildenafil (Viagra ) [12] and vardenafil (Levitra ) [13], has an improved PDE5/PDE6 selectivity compared to sildenafil [14-16]. Tadalafil (Cialis ) is a newly approved oral selective PDE5 inhibitor indicated for the treatment of ED. 

More recently, a highly selective, sensitive, and rapid HPLC method has been developed and validated to quantify tadalafil in human plasma [44]. The tadalafil and internal standard (loratadine, I.S.) were extracted by liquid-liquid extraction technique followed by an aqueous back-extraction allowing injection of an aqueous solvent in the HPLC system. The chromatographic separation was performed on a reverse phase BDS Hypersil C18 column (250 mm x 4.6 mm, 5 pm. Thermo Separation Co., USA) with a mobile phase of acetonitrile and aqueous solution containing 0.012 M... 

A more simple, rapid, sensitive, and specific liquid chromatography, tandem mass spectrometry method [46], was developed and validated for quantitation of tadalafil 1 in human plasma, a new selective, reversible... 

A high performance liquid chromatographic method was developed for the chiral separation of new selective PDE5 inhibitors, tadalafil and its three isomers [47]. The chiral separation was performed on a Chiralpak AD column. The mobile phase was hexane-isopropyl alcohol (1 1, v/v). UV detection was at 220 nm. Baseline chiral separation for the four isomers was obtained within 30 min. Each of the resolutions of the two pairs enantiomers were more than 2.0. The limits of quantitation were 0.60, 0.90, 1.20, and 1.80 ng for (6R,12aS), (6R,12aR), (6S, 12aS), and (6S,12aR) isomers, respectively. Relative standard deviation of the method was below 2% (n = 5). The method is suitable in quality control. 

Tadalafil is a potent and selective PDE5 inhibitor imder regulatory review for the treatment of ED. In a clinical trial, tadalafil showed a clinical response in erectile function for up to 24 h postdosing. 

Item(s) allowable on the NHS Yes, see Drug Tariff. The medication ordered indicates that the patient is diabetic therefore tadalafil may be prescribed under the selected list scheme. Return the prescription to the prescriber to ask him to add SLS to the body of the prescription next to the order for Cialis so that it will be passed for payment by the PPD. 

As indicated earlier, the selective PDE5 inhibitors developed for the treatment of male erectile dysfunction resulting from organic or mixed organic-psychogenic origin have been the most successful PDE inhibitors. The three marketed drugs are sildenafil, vardenafil, and tadalafil (Fig. 17.2). In addition to the treatment of erectile dysfunction, sildenafil has been indicated for the treatment of pulmonary hypertension and female sexual dysfunction. These latter uses are unlabeled uses. 

A comparison of the in vitro inhibition values (ICsos) reveals that vardenafil is approximately 10 times more selective as an inhibitor of PDE5 than sildenafil and tadalafil (Table 45.6) (140). Furthermore,... 

A double-blind, placebo-controlled, randomised, crossover study in 17 healthy subjects given enough oral theophylline (a non-selective phosphodiesterase inhibitor) to achieve steady-state levels of about 12 mg/L found that the concurrent use of tadalafil 10 mg daily for 7 days did not affect the pharmacokinetics of either drug. There was a small increase of 3.5 bpm in the heart rate, which was not considered to be clinically relevant in the healthy subjects, but the UK manufacturers advise that this should be considered when both drugs are used concurrently. ... 

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