Tadalafil Alcohol

Drugs that may interact with nitrates include alcohol, alteplase, aspirin, beta-blockers, calcium channel blockers, dihydroergotamine, heparin, nondepolarizing muscle relaxants, phenothiazines, phosphodiesterase inhibitors (eg, sildenafil, tadalafil, vardenafil), and vasodilators. 

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 pharmacokinetics in patients with ED showed linear relation with respect to dose and duration of treatment, and a one-compartment model adequately described the data. The absorption rate was rapid (1.86 h ), and the t)q)ical population estimates of the apparent oral clearance (CL/F) and apparent volume of distribution were 1.6 L/h and 63.8 L, respectively. Disposition parameters showed a moderate degree of interindividual variability (39-45%). The value of CL/F decreased slightly with increasing serum y-glutamyl transferase (GGT) concentration, the only statistically significant covariate detected. Systemic exposure to tadalafil was not influenced by age, weight, smoking status, alcohol consumption, liver enz nne status, ED severity, cardiovascular condition, or diabetes mellitus. 

Tadalafil is different in structure from both sildenafil and vardenafil. It is rapidly absorbed and peaks in concentration (378 pg/L after a 20-mg dose) after 2 hours, displaying a long half-life of 17.5 hours. It also is metabolized by the liver (CYP3A4). Notably, its pharmacokinetics is not clinically influenced by alcohol or food intake or by factors such as diabetes or impaired hepatic or renal function (13). 

Studies in subjects given alcohol 0.6 or 0.7 g/kg found that the effect of alcohol on blood pressure was unchanged by tadalafil 20 mg, although some subjects experienced dizziness and postural hypotension. In addition, the effects of alcohol on cognitive function were unchanged by tadalafil 10 mg. The pharmacokinetics of tadalafil 10 or 20 mg and alcohol were also unaffected by concurrent use. However, the manufacturers say that because both alcohol and tadalafil can cause peripheral vasodilation, additive blood pressure lowering effects are possible, especially with substantial amounts of alcohol (5 units) and the US manufacturer states that this may result in postural hypotension, increased heart rate, dizziness and headaehe. Aleohol may also affect the ability to have an erection. ... 

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