Comparative pharmacodynamics of intranasal and enteral administration of captopril for uncomplicated hypertensive crises
Keywords:hypertensive crises, captopril gel, intranasal administration
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.
Ostrovskaya, Yu. I., & Melekhov, A. V. (2017). Gipertonicheskii kriz – taktika vedeniya i predotvrashcheniya [A hypertension stroke is tactics of conduct and prevention]. Atmosfera. Novosti kardiologii, (3), 47-52. [in Russian].
Kryukov, E. V., Potekhin, N. P., Fursov, A. N., Chernetsov, V. A., Chernov, S. A., & Zakharova, E. G. (2016). Gipertonicheskii kriz: sovremennyi vzglyad na problemu i optimizatsiya lechebno-diagnosticheskikh podkhodov [Hypertensive crisis: modern view of the problem and optimization of diagnostic and therapeutic modalities]. Klinicheskaya Meditsina, 94(1), 52-56. [in Russian]. https://doi.org/10.18821/0023-2149-2016-94-1-52-56
Ambrosova, T. M., & Ashcheulova, T. V. (2018). Menedzhment neoslozhnennogo gipertenzivnogo kriza v praktike semeinogo vracha [Uncomplicated hypertensive crisis management in family practice]. Mizhnarodnyi medychnyi zhurnal, (1), 16-19. [in Russian].
(2012). Unifikovanyi klinichnyi protokol medychnoi dopomohy. Arterialna hipertenziia, pervynna medychna dopomoha (dohospitalnyi etap), vtorynna (spetsialisovana) pervynna medychna dopomoha (2012 rik) [Compatible clinical protocol of medicare. hyperpiesis, primary medicare (before the hospital stage) secondary (specialized) medicare]. Arterialnaya gipertenziya, (1), 67-95. [in Ukrainian].
Sottiev, B. G., Abdullazhanov, F. G., Makhmudov, K. A. & Kuchkarova, F. E. (2019). Neotlozhnaya pomoshch u bolnykh s gipertonicheskimi krizami na dogospitalnom etape [First aid for patients with hypertension strokes on the before the hospital stage]. Evraziiskii kardiologicheskii zhurnal, (2), 67-68. [in Russian].
Crowe, T. P., Greenlee, M., Kanthasamy, A. G., & Hsu, W. H. (2018). Mechanism of intranasal drug delivery directly to the brain. Life sciences, 195, 44-52. https://doi.org/10.1016/j.lfs.2017.12.025
Bailey, A. M., Baum, R. A., Horn, K., Lewis, T., Morizio, K., Schultz, A., Weant, K., & Justice, S. N. (2017). Review of Intranasally Administered Medications for Use in the Emergency Department. The Journal of emergency medicine, 53(1), 38-48. https://doi.org/10.1016/j.jemermed.2017.01.020
Alshweiat, A., Ambrus, R., & Csoka, I. (2019). Intranasal Nanoparticulate Systems as Alternative Route of Drug Delivery. Current medicinal chemistry, 26(35), 6459-6492. https://doi.org/10.2174/0929867326666190827151741
Lochhead, J. J., Wolak, D. J., Pizzo, M. E., & Thorne, R. G. (2015). Rapid transport within cerebral perivascular spaces underlies widespread tracer distribution in the brain after intranasal administration. Journal of cerebral blood flow and metabolism, 35(3), 371-381. https://doi.org/10.1038/jcbfm.2014.215
Lokhande S. S. (2018). A Review on Intranasal Drug Delivery System with Recent Advancement. Research Journal of Topical and Cosmetic Sciences, 9(1), 12-18. https://doi.org/10.5958/2321-5844.2018.00004.3
Xu, Y., Wei, L., & Wang, H. (2020). Progress and perspectives on nanoplatforms for drug delivery to the brain. Journal of Drug Delivery Science and Technology, 57. https://doi.org/10.1016/j.jddst.2020.101636
Patel, A. A., Patel, R. J., & Patel, S. R. (2018). Nanomedicine for Intranasal Delivery to Improve Brain Uptake. Current drug delivery, 15(4), 461-469. https://doi.org/10.2174/1567201814666171013150534
Kumar, H., Mishra, G., Sharma, A. K., Gothwal, A., Kesharwani, P., & Gupta, U. (2017). Intranasal Drug Delivery: A Non-Invasive Approach for the Better Delivery of Neurotherapeutics. Pharmaceutical nanotechnology, 5(3), 203-214. https://doi.org/10.2174/2211738505666170515113936
Demina, N. B., Bakhrushina, E. O., Bardakov, A. I. & Krasnyuk, I. I. (2019). Biofarmatsevticheskie aspekty dizaina intranazal'nykh lekarstvennykh form [Design of intranasal dosage forms: biopharmaceutical aspects]. Farmatsiya, (3), 12-17. [in Russian]. https://doi.org/10.29296/25419218-2019-03-02
Abdullakh, A. Zh. (2014). Rozrobka skladu ta tekhnolohii miakykh likarskykh zasobiv z kaptoprylom dlia terapii arterialnoi hipertenzii [Development of composition and technology of semisolid medications with captopril for therapy of arterial hypertensia (Doctoral PhD dissertation)]. Zaporizhzhia State Medical University, Zaporizhzhia. [in Ukrainian].
Gladychev, V. V., Abdullah, A. Zh., Lisyanskaya, A. P., Kechin, I. L., & Biryk, I. A. (2013). Izuchenie vliianiia osnov-nositelei na intensivnost vysvobozhdeniia kaptoprila iz nasalnykh miagkikh lekarstvennykh form [Study of ointment base infl uence over intensity of captopril release from nasal semisolid dosage forms]. Kubanskii nauchnyi meditsinskii vestnik, (5), 69-73. [in Russian].
How to Cite
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access)