[Pharmacokinetic features of sildenafil spray in healthy men depending on food intake].

AIM: In order to evaluate the bioequivalence and benefits of a new dosage form of the type 5 phosphodiesterase inhibitor, sildenafil, two open-label studies in healthy male volunteers were carried out. MATERIALS AND METHODS: An open, randomized, crossover study to compare the pharmacokinetics after a single dose of sildenafil at a dosage of 50 mg on an empty stomach in a new spray form (test drug) and in a traditional tablet form (comparison drug) on 44 volunteers (18 to 43 years old) was done. To assess the effect of food intake on pharmacokinetics, an open, non-randomized study was conducted on 6 healthy male volunteers (from 23 to 35 years old) who received sildenafil (50 mg) after a meal in timely fashion: 1) spray, under the tongue, without drinking, 2) spray , in the mouth, drinking water and 3) the tablet form, drinking water. For pharmacokinetic analysis, blood was analyzed for 24 hours. Plasma concentration of sildenafil was determined by high performance liquid chromatography with tandem mass spectrometric detection (HPLC/TM/SD). The main parameters were the rate (maximum concentration; Cmax) and the degree of absorption (area under the pharmacokinetic curve "concentration-time" during the observation period; AUC0-t) after a single dose of drugs. In addition, the pharmacokinetic profiles of the bioavailability of sildenafil and its active metabolite, N-desmethyl sildenafil, as well as the safety of the different dosage forms, were evaluated. RESULTS: When comparing taking drugs on an empty stomach, the 90% confidence intervals (CI) of the ratios of the mean Cmax and AUC0-t values of sildenafil were 82-106% and 82-101%, respectively. An earlier achievement of the maximum concentration of sildenafil was detected when taking the test drug compared with the standard form (51 and 62 minutes, respectively, Z-value=-2.25, p-value=0.0244). In addition, it was shown that when taking Viagra after a meal, the determination of sildenafil in plasma was delayed (after 30 minutes) compared to the tested drugs (after 10 minutes), however, significant differences in Tmax between the dosage forms were not seen. In two studies, most adverse events were mild to moderate and resolved uneventfully. DISCUSSION: The bioavailability of the new dosage form, the sildenafil spray, is equivalent to the traditional form, however, it has an advantage in terms of onset of action. For example, when taking a spray, an earlier achievement of the maximum concentration of sildenafil and an earlier detection of sildenafil in plasma are shown compared to the traditional tablet form. CONCLUSIONS: Our results suggest that the new dosage form of sildenafil is a reliable alternative therapeutic option for the treatment of erectile dysfunction.

[Results of endovascular treatment of acute tandem occlusion of internal carotid and middle cerebral arteries]. / Rezul'taty endovaskulyarnogo lecheniya ostroi tandemnoi okklyuzii vnutrennei sonnoi i srednei mozgovoi arterii.

OBJECTIVE: To evaluate the results of endovascular treatment of patients with ischemic stroke caused by acute tandem occlusion of the internal carotid and middle cerebral arteries (ICA and MCA). MATERIAL AND METHODS: Endovascular intervention was performed in 8 patients with tandem occlusion of ICA and MCA. The neurological deficit on admission was 17.4±5.6 NIHSS points and the average ASPECTS score was 9.5±0.8. The time from the onset of neurological symptoms to reperfusion was 224±68 min. Thrombolytic therapy was initiated before brain revascularization and continued intraoperatively in 4 out of 8 patients. ICA stenting after aspiration thrombectomy was required in 6 patients. Both antegrade (n=4) and retrograde (n=2) methods of brain revascularization were used. RESULTS: The rate of detection of tandem lesion in patients with ischemic stroke who underwent endovascular treatment was 5.4%. Technical success in restoring blood flow in the ICA basin at extra-and intra-cranial levels (mTICI 2b/3) was achieved in 7 (87.5%) patients. Intracranial hemorrhagic complications that affected the outcome of the disease were clinically significant in 25% of patients (n=2). The mortality rate was 37.5% (n=3). A satisfactory clinical result (a deficit of 0-2 mRS scores) was achieved at discharge in one of 5 surviving patients. CONCLUSION: Further studies of choosing the optimal surgical tactics for tandem occlusion of ICA and MCA, taking into account its effectiveness and safety, are need.