Clinical pharmacology of drugs in their intravaginal administration

Talibov O.B.

A.I. Evdokimov Moscow State University of Medicine and Dentistry, Ministry of Health of Russia, Moscow, Russia
The paper deals with the characteristics of the intravaginal route of drug administration that is attractive from two points of view. Firstly, this is the ability to quickly deliver the drug directly into the disease focus. Secondly, the characteristics of the vaginal epithelium (a low metabolic activity against xenobiotics), the relatively favorable aqueous medium for acid-resistant molecules, good organ vascularization, and the entry of absorbed substances into the bloodstream, by passing the liver, create favorable conditions for the use of systemic drugs. Currently, there are many vaginal drug delivery systems: solutions, creams, ointments, gels, tampons, suppositories, capsules, pessaries, sponges, and modified-release vaginal devices (e.g. rings) Despite the ease of use, the vaginal route of drug administration can be associated with certain features, such as differences in the thickness of the mucous membrane in different phases of the menstrual cycle and in different periods of life, variations in the pH of vaginal secretion, the likelihood of dosage form leakage, the effect on the vaginal mucosa and local microbiocenosis, probable discomfort when using certain formulations. The paper describes the anatomical and histological features of the vagina, which affect the absorption of various substances and provides information on the pharmacokinetics of drugs, including those prescribed for the treatment of vaginal infections.
Conclusion. Despite its many features, intravaginal administration is one of the most common and widely studied methods of drug delivery. When drugs are prescribed, it is necessary to take into account their pharmacokinetic differences that are observed in both different periods of female patient’s life and different phases of the menstrual cycle, and the associated possible fluctuations in the systemic concentration of drugs. The latter used to achieve an exclusively local effect should be characterized by a minimal systemic absorption and a minimal impact on local immunity and natural vaginal biocenosis.

Keywords

intravaginal administration
pharmacokinetics
vaginal infections

References

  1. Macht D.I. On the absorption of drugs and poisons through vagina. J. Pharmacol. Exp. Ther. 1918; 10(7): 509-22.
  2. Rock J., Barker R.H., Bacon W.B. Vaginal absorption of penicillin. Science. 1947; 105(2714): 13. https://dx/doi/org/10.1126/science.105.2714.13.
  3. Patel L.G., Warrington S.J., Pearson R.M. Propranolol concentrations in plasma after insertion into the vagina. Br. Med. J. (Clin. Res. Ed). 1983; 287(6401): 1247-8. https://dx/doi/org/10.1136/bmj.287.6401.1247.
  4. De Ziegler D., Bulletti C., De Monstier B., Jaaskelainen A.S. The first uterine pass effect. Ann. N. Y. Acad. Sci. 1997; 828: 291-9. https://dx/doi/org/10.1111/j.1749-6632.1997.tb48550.x.
  5. Paavonen J. Physiology and ecology of the vagina. Scand. J. Infect. Dis. 1983; 40(Suppl.): 31-5.
  6. Молчанов О.Л., Кира Е.Ф. Микроэкосистема влагалища. Особенности функционирования в норме. Акушерство и гинекология Санкт-Петербурга. 2018; 1: 65-8. [Molchanov O.L., Kira E.F. Microecosystem of the vagina. Features of normal functioning. Obstetrics and gynecology of Saint Petersburg. 2018; 1: 65-8. (in Russian)].
  7. Stanek R., Gain R.E., Glover D.D., Larsen B. High performance ion exclusion chromatographic characterization of the vaginal organic acids in women with bacterial vaginosis. Biomed. Chromatogr. 1992; 6(5): 231-5. https://dx/doi/org/10.1002/bmc.1130060506.
  8. Choudhury A., Das S., Kar M. A review on novelty and potentiality of vaginal drug delivery. Int. J. Pharm. Technol. Res. 2011; 3(2): 1033-44.
  9. Katz D.F., Dunmire E.N. Cervical mucus. Problems and opportunities for drug delivery via the vagina and cervix. Adv. Drug Deliv. Rev. 1993; 11(3): 385-401.
  10. Huang S.M., Lertora J.J.L., Markey S.P., Atkinson A.J. Jr., eds. Atkinson’s principles of clinical pharmacology. 3rd ed. Elsevier; 2012.
  11. Woolfson A.D., Malcolm R.K., Gallagher R. Drug delivery by the intravaginal route. Crit. Rev. Ther. Drug Carrier Syst. 2000; 17(5): 509-55.
  12. Chen S.C., Lewis R.E., Kontoyiannis D.P. Direct effects of non-antifungal agents used in cancer chemotherapy and organ transplantation on the development and virulence of Candida and Aspergillus species. Virulence. 2011; 2(4): 280-95. https://dx/doi/org/10.4161/viru.2.4.16764.
  13. Тихомиров А.Л., Олейник Ч.Г. Рациональная терапия кандидозного и смешанного вульвовагинитов. Сonsilium medicum. 2005; 7(3): 214-7. [Tikhomirov A.L., Oleinik Gh.G. Rational therapy of candida and mixed vaginitis. Consilium medicum. 2005; 7 (3): 214-7. (in Russian)].
  14. Jakab Á., Mogavero S., Förster T.M., Pekmezovic M., Jablonowski N., Dombrádi V. et al. Effects of the glucocorticoid betamethasone on the interaction of Candida albicans with human epithelial cells. Microbiology (Reading). 2016; 162(12): 2116-25. https://dx/doi/org/10.1099/mic.0.000383.
  15. Wang F.J., Liu Z.H., Wu W.X., Bai H.H., Dong H.Y. Species distribution and in vitro antifungal susceptibility of vulvovaginal Candida isolates in China. Chin. Med. J. (Engl.). 2016; 129(10): 1161-5. https://dx/doi/org/10.4103/0366-6999.181964.

Received 03.12.2020

Accepted 14.12.2020

About the Authors

Oleg B. Talibov, Cand. Sci. (Med.), associate professor Therapy, Clinical Pharmacology and Ambulance Care Department, A.I. Evdokimov Moscow State University of Medicine and Dentistry. ORCID: 0000-0001-6381-2450.127473, Russia, Moscow, Delegatskaya str., 20-1.

For citation: Talibov O.B. Clinical pharmacology of drugs in their intravaginal administration.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2020; 12: 194-198 (in Russian)
https://dx.doi.org/10.18565/aig.2020.12.194-198

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