Comparative pharmacodynamics of intranasal and enteral administration of captopril for uncomplicated hypertensive crises

Abstract

Uncomplicated hypertensive crises without acute or progressive damage to the target organs pose a potential threat to the patient’s life and require rapid reduction of arterial pressure within hours or days in an outpatient setting. The existing protocol for the treatment of this pathology is not entirely perfect, as it does not offer the primary physician a clear and unambiguous description of the use of effective and complementary drugs. The use in these cases of nasal transport of antihypertensive active pharmaceutical ingredients in appropriate dosage forms makes it possible to ensure their rapid delivery to the bloodstream and perivascular structures of the brain.

Based on previous experience, and taking into account biopharmaceutical research on pharmacodynamics and pharmacokinetics of captopril innovative captopril dosage form has been developed and put into practice for trasmucosal administration as 2.5 % intranasal gel with controlled releasing of captopril substance in Zaporizhzhia State Medical University.

The aim of the research was to study the pharmacodynamics of captopril gel in patients with arterial hypertension with uncomplicated hypertensive crises.

Materials and methods. 58 outpatients with stage 2 arterial hypertension with uncomplicated cardiac crises were surveyed, an experienced group had 30 patients aged from 38 to 69 years (average age 52.60 ± 5.03 years) with average duration of disease 11.50 ± 2.72 years, obtained the intranasal application into two nasal routes 0.5 ml 2.5 % captopril gel with a dose syringe. Comparison group had 28 patients with stage 2 arterial hypertension with uncomplicated cardiac crises aged from 37 to 65 years with duration of arterial hypertension 10.8 ± 2.63 years, obtained peroral captopril in equivalent dose. Captopril tablets 0.025 g were used as a reference drug. In the course of treatment, the indicators of office blood pressure and heart rate in the crisis state were determined after 60, 120 and 240 minutes after the use of captopril. Because of asymmetric distribution, the non-parametric method – the Wilcoxon signed-rank test – was used.

Results. There has been a significant reduction in systolic and diastolic arterial pressure one hour after the gel’s intranasal application by 19.9 % and 23.8 % respectively, whereas, after the use of captopril in tablets, there is only a tendency to decrease systolic and diastolic pressures by 8.8 % and 11.6 % respectively. Two hours after the use of the gel, systolic and diastolic blood pressure decreased by 23.5 % and 23.5 % respectively, reaching the level recommended by the leading cardiologists of Ukraine. After oral administration of the captopril tablets, systolic arterial pressure decreased by 13 %, diastolic arterial pressure, and heart rate showed only a downward trend. Four hours after the use of the captopril gel, there was a gradual increase in systolic arterial pressure, and the level of diastolic arterial pressure remained almost the same. After application of captopril gel, the heart rate in the treatment dynamics remained unchanged, with a trend of acceleration in the first time of treatment, and decreased by 4 hours by 12.4 %.

Conclusions. A randomized, controlled study of nasal captopril pharmacodynamics in the form of 2.5 % hydrophilic gel compared to its tableted dosage form in patients with arterial hypertension with uncomplicated hypertensive crises was carried out. It has been established that the nasal dosage form of captopril provides for the reduction of the arterial pressure to the level recommended in the case of uncomplicated hypertensive crises for 4 hours more efficiently than the oral agent. Captopril nasal gel has been shown to have good tolerance and there are practically no side effects from its use.