raw material Acetildenafil was originally a drug for the treatment of angina pectoris developed and produced by Pfizer company in the United States. In clinical trials, it was found that its effect in the treatment of angina pectoris is general, but it has a special effect in the treatment of impotence. This unexpected discovery prompted the manufacturer to simply declare with drugs for the treatment of impotence. The US Food and Drug Administration (FDA) officially approved the drug as a special drug for the treatment of impotence on March 27, 1997.
What is the situation of the hongdenafil in various countries?
Acetildenafil (hongdenafil) is a synthetic drug that acts as a phosphodiesterase inhibitor. It is an analog of sildenafil (Viagra) which has been detected in numerous different brands of supposedly herbal aphrodisiac products sold to boost libido and alleviate erectile dysfunction. The action principle of red dinafil is equivalent to sildenafil, and the addition amount is slightly less than sildenafil. It was once known as sildenafil and cannot be detected. Acetildenafil is modified on the basis of sildenafil citrate. The action principle of red Acetildenafil is equivalent to sildenafil citrate, and the addition amount is slightly less than sildenafil citrate. The design analogs of such Licensed PDE 5 inhibitors (such as sildenafil and vardenafil) are obviously designed to avoid the legal restrictions on the sale of erectile dysfunction drugs in western countries because general PDE 5 inhibitors are prescription drugs and protected by patents in most western countries, However, there is an exception to patent protection, which allows others to develop new products based on the original products. Based on the further development of sildenafil and other products, hongdenafil is refined and processed to prove the existence of PDE 5 inhibitory activity in vitro. It also has the same effect in animal experiments, so it has become a substitute product in the future. However, when the product has not completed the testing process and has not submitted the patent application process, it is popular all over the world, which not only circumvents the relevant laws but also brings convenience to the ambiguity of the product. However, because of its unknown results, it also poses a major health risk, so do not use it without permission.
What is the pharmacokinetics of Acetildenafil?
The absorption of Acetildenafil is rapid after oral administration, and the absolute bioavailability is about 40%. Its pharmacokinetic parameters are proportional to the dose within the recommended dose range. It mainly eliminates liver metabolism (cytochrome P450 isoenzyme 3A4 pathway) and generates an active metabolite, whose properties are similar to those of sildenafil. When powerful inhibitors of cytochrome P450 isoenzyme 3A4(CYP450 3A4) such as erythromycin, ketoconazole, and itraconazole and nonspecific inhibitors of cytochrome P450(CYP450) such as cimetidine and sildenafil are used together, it may be possible The elimination half-life of Acetildenafil and its metabolites are about 4 hours. When given 25 ~ 100 mg on an empty stomach, the maximum plasma concentration (Cmax) reached 127 ~ 560 ng/ml within about 1 hour. The selectivity of Acetildenafil or its main metabolite N- desmethyl to PDE5 is about 50%, and the protein binding rate is 96%. At the maximum plasma concentration of total Acetildenafil, the Cmax of free Acetildenafil is 22ng/ml. After oral or intravenous administration, Hongdinafei is mainly excreted from feces in the form of metabolites (about 80% of the oral dose), and a small amount is excreted from urine (about 13% of the oral dose).
Pharmacokinetics of special population: the elderly: the clearance rate of sildenafil in healthy elderly volunteers (≥ 65 years old) decreased, and the free blood concentration was about 40% higher than that in young healthy volunteers (18-45 years old). Sildenafil citrate bottled renal insufficiency: volunteers with mild (creatinine clearance equal to 50-80ml / min) and moderate (creatinine clearance equal to 30-49ml / min) renal damage had no change in the pharmacokinetics of a single oral dose of sildenafil 50mg. In volunteers with severe renal damage (creatinine clearance ≤ 30ml / min), the clearance of sildenafil decreased, and the area under the drug time curve (AUC) and Cmax almost doubled compared with volunteers in the same age group without renal damage.
Liver dysfunction: Sildenafil clearance decreased in volunteers with cirrhosis (Child-Pugh grade A and b), and AUC and Cmax increased by 84% and 47% respectively compared with volunteers without liver damage in the same age group. Therefore, over 65 years old, liver function damage and severe renal function damage will lead to an increase in plasma sildenafil level. The starting dose for this kind of patient should be 25mg
Comparison of pharmacokinetics between Acetildenafil and other similar products
The half inhibition rate (IC50), titer intensity, and selectivity of phosphodiesterase. The half inhibition rate of Acetildenafil for phosphodiesterase-5 was 7.6 nanomoles (nm). Compared with sildenafil, its relative titer intensity was (1:1). At the same time, phosphodiesterase-6 can also be inhibited by Acetildenafil. For the convenience of comparison, the parameters of Acetildenafil and other sildenafil analogs are shown in the table below. Among them, sildenafil is the parent value of relative values. When the relative titer intensity is less than one, the drug is more potent than its mother drug. It should be noted that when there are multiple values in a cell, it indicates that the data provided by different works of literature are different from each other, and the compounds in the table are measured in the dosage form of supplements. In the table, there are few relevant data on sildenafil, vardenafil, and tadalafil, and the existing data are measured from the in vitro inhibition test of phosphodiesterase-5 and phosphodiesterase-6. Since the safety and efficacy of sildenafil analogs have not been supervised and evaluated, its preclinical pharmacological parameters and toxicity are not clear. It can be seen from the table that the relative titer intensity of some analogs is much higher than that of sildenafil.
Drug molecule | Half inhibition rate of phosphodiesterase-5 | relative potency | Half inhibition rate of phosphodiesterase-6 | relative potency |
Sildenafil | 6.6 nM 7.1 nM 6.86 nM 7.2 nM 3.6 nM 4.3 nM | 1 | 15 nM | 1 |
Benzamidenafil | 1.1 nM | 0.26 | 20 nM | 1.33 |
Hydroxy haomosi sildenafil | 1.9 nM 3.4 nM | 0.52 0.48 | ||
Piperidine sildenafil | 5.8 nM | 1.6 | ||
Thioquinapiperifil | Ki 0.16 mM | 0.02 | ||
Acetildenafil | 7.6 nM | 1.1 | ||
Having sildenafil | 3.8 nM | 0.53 | ||
This sildenafil | 0.59 nM | 0.09 | 60 nM | 4 |
Vardenafil | 0.7 nM | 0.11 | ||
Tadalafil | 5.0 nM | 0.70 |
Toxicity to date, sildenafil's analogs are non-toxic, but some risks that may lead to toxicity have been documented. For example, it is possible that the dose of sildenafil reaches 60 mg per capsule. In the inhibition test of phosphodiesterase-6 in vitro (concentration range: 0.030 to 30 Nanomole) by Ballard et al. Acetildenafil inhibited phosphodiesterase-6 in bovine retina, and this antagonistic mechanism has been pointed out in many kinds of literature to be positively correlated with visual impairment.
Side effects so far, there is no clinical side effect data of sildenafil analogs. However, piecemeal clinical cases can provide some references for its side effects. For example, in many academic kinds of literature, patients often develop side effects when aphrodisiac herbs containing sildenafil analogs are taken. In Hong Kong, a 28-year-old male patient developed ataxia symptoms such as gait instability after taking a supplement containing Acetildenafil for eight consecutive days.