Comparative analysis of pharmacokinetic parameters of transdermal and intramuscular administration of Galavit®

Introduction. Immunomodulator Galavit® is a promising domestic drug for the prevention and treatment of various infectious diseases. Earlier, the authors have developed and investigated in vitro its new dosage form – transdermal therapeutic system (TTS). Positive results from experiments made it possible to proceed to the study of the pharmacokinetic parameters of Galavit® TTS in animals.

Objective: to compare the pharmacokinetic parameters of intramuscular and transdermal administration of immunomodulator Galavit® in animal experiments.

Materials and methods. Sodium aminodihydrophthalazinedione was used as a substance in the form of a powder to prepare a solution for intramuscular administration of 100 mg (trade name Galavit®, manufacturer SELVIM LLC). The pharmacokinetics of transdermal and intramuscular injections were studied in male Chinchilla rabbits weighing 4.5–5.0 kg. Serum sodium aminodihydrophthalazinedione concentrations in animals were determined by highperformance liquid chromatography using a specially developed technique.

Results. In contrast to the injection method, a prolonged and uniform inflow of the drug substance (MP) into the body is observed for percutaneous administration of sodium aminodihydrophthalazinedione. The maximum serum Galavit® concentration for a 40 mg dose (0.172 ± 0.054 μg/mL) and for a 80 mg dose (1.16 ± 0.22 μg/mL) remained at a constant level for 9 and 8 hours, respectively. The relative bioavailability of the Galavit® transdermal therapeutic system was 0.65 and 1.06 for the same doses.

Conclusion. Application of Galavit® 80 mg transdermal therapeutic system provides bioavailability that is similar to the intramuscular administration of this drug at the same dose. At the same time, its maximum serum concentration significantly decreases and the retention time of Galavit® in the body increases by more than 10 times, which can contribute to prolongation of the drug effect. Due to the current growing interest in the use of immunomodulator Galavit® for coronavirus infection COVID-19, the development and study of a new dosage form is a promising task

1. Sampiev AM, Nikiforova EB, Davitavjan NA. Sovremennye dostizhenija v razrabotke i primenenii innovacionnyh lekarstvennyh sredstv. Novye tehnologii. 2012; 2: 247–254. [In Russ, English abstract].

2. Леонова МВ. Новые лекарственные формы и системы доставки лекарственных средств: особенности пероральных лекарственных форм. Часть 1. Лечебное дело. 2009; 2: 21–31. Leonova MV. Novye lekarstvennye formy i sistemy dostavki lekarstvennyh sredstv: osobennosti peroral’nyh lekarstvennyh form. Chast’ 1. Lechebnoe delo. 2009; 2: 21–31. [In Russ].

3. Vasil’ev AE, Krasnjuk II, Ravikumar S, Tohmahchi VN. Transdermal’nye terapevticheskie sistemy dostavki lekarstvennyh veshhestv (obzor). Himiko-farmacevticheskij zhurnal. 2001; 35: 29–42. [In Russ].

4. Beregovyh VV, Pjatigorskaja NV, Prudkevich JuA, Kedik SA. Transdermal’nye terapevticheskie sistemy dostavki lekarstvennyh sredstv. Vestnik MITHT, 2012; 7 (5): 17–22. [In Russ].

5. HaitovRM. Immunomoduljatory: mify i real’nost’. Immunologija. 2020; 41 (2): 101–106. [In Russ]. doi: 10.33029/0206-4952-2020-41-2-101-106.

6. Djadina KS, Zemskov AM, Berezhnova TA, Mihajlova MD, Zemskova VA, Dobrosockih GV. Perspektivy immunoterapii gnojnovospalitel’nyh zabolevanij. Vestnik novyh medicinskih tehnologij. Jelektronnoe izdanie. 2020; 2: 81–89. [In Russ, English abstract]. doi: 10.24411/2075-4094-2020-16625.

7. Luss LV, Martynov-Radushinskij AA. Vtorichnaja immunnaja nedostatochnost’. Vsegda li nuzhny immunomoduljatory? Medicinskij sovet. 2014; 2: 40–45. [In Russ]. doi: 10.21518/2079-701X-2014-2-40-45.

8. Sologub TV, Osinovec OJu. Primenenie immunomodulirujushhego preparata galavit v kompleksnoj terapii grippa. Klinicist. 2012; 2: 76–80. [In Russ, English abstract].

9. Rumjancev AG, Shherbina AJu. Jeffektivnost’ preparata galavit u chasto i dlitel’no bolejushhih detej starshe 6 let. Rossijskij vest nik perinatologii i pediatrii. 2008; 6: 100–101. [In Russ, English abstract].

10. Kuznecova EG, Kuryleva OM, Salomatina LA, Sevast’janov VI. Jeksperimental’noe issledovanie diffuzii immunomoduljatora Galavit® v model’noj sisteme. Razrabotka i registracija lekarstvennyh sredstv. 2020; 9 (1): 92–97. [In Russ, English abstract]. doi: 10.33380/2305-2066-2020-9-1-92-97.

11. Kuznecova EG, Kuryleva OM, Salomatina LA, Sevast’janov VI. Primenenie sinteticheskoj i biologicheskoj test-sistem pri razrabotke transdermal’nyh terapevticheskih sistem. Perspektivnye materialy. 2020; 8: 49–59. [In Russ, English abstract]. doi: 10.30791/1028-978X-2020-8-49-58.

12. Rukovodstvo po provedeniju doklinicheskih issledovanij lekarstvennyh sredstv. Chast’ pervaja / Pod red. A.N. Mironova. M.: Grif i K, 2012. 944 s.

13. Farmacevticheskaja razrabotka: koncepcija i prakticheskie rekomendacii. Nauchno-prakticheskoe rukovodstvo dlja farmacevticheskoj otrasli. Pod red. S.N. Bykovskogo. М.: Pero, 2015.

14. Zherdev VP, Voronina TA, Garibova TL, Kolyvanov GB, Litvin AA, Sariev AK i dr. Ocenka farmakokinetiki i jeffektivnosti fenazepama u krys pri transdermal’nom i jenteral’nom sposobah vvedenija. Jeksperimental’naja i klinicheskaja farmakologija. 2003; 66 (1): 50–53. [In Russ].

15. Narasimha Murthy S, Hiremath SR. Clinical pharmacokinetic and pharmacodynamic evaluation of transdermal drug delivery systems of salbutamol sulfate. Int J Pharm. 2004; 287 (1–2): 47–53.

16. Basok YB, Salomatina LA, Tikhobaeva AA, Sevastianov VI. A Pharmacokinetic Study of Caffeine Transdermal Therapeutic Systems. Advanced Metals, Ceramics and Composites (ed. H. Tu, K. Solntsev, R. Zhou), Yunnan Publ. Group Corp., Kunming, China. 2013: 175–177.

17. Sergienko VI, Bondareva IB. Matematicheskaya statistika v klinicheskikh issledovaniyakh. M.: GEOTAR-MED, 2001: 256.

18. Kolesov SV, Gorbatjuk DS, Panteleev AA, Bernakevich AI, Ukolov KJu. Profilaktika srednih i tjazhelyh form COVID-19 aminodigidroftalazindionom natrija (Galavit®) u medicinskogo personala «krasnoj zony». Immunologija. 2020; 41 (6): 527–539. [In Russ]. doi: 10.33029/0206–4952-2020-41-6-527-539.