Preview

Сибирский научный медицинский журнал

Advanced search

Studying the pharmacokinetic parameters of new normothymic drug based on the complex of lithium citrate, aluminum oxide and polymethylsiloxane

https://doi.org/10.15372/SSMJ20190602

Abstract

For the treatment of bipolar affective disorders, lithium preparations are the most famous and effective. But the main problem with the use of lithium preparations is the narrow «therapeutic corridor». An urgent task is the creation of dosage forms of lithium with a slow release and a wide therapeutic range. The study object was a new normotymic drug based on lithium, aluminum oxide and polymethylsiloxane. Due to the new carrier matrix lithium is released from its porous structure gradually providing a prolonged effect and maintaining an optimal concentration in the blood which also helps to minimize side effects. The purpose of the study was to explore the pharmacokinetic parameters of a normotymic drug based on a complex lithium citrate, aluminum oxide and polymethylsiloxane (LOAP).

Material and methods: for the assessment of pharmacokinetic parameters the method of atomic emission spectrometry with inductively coupled plasma and two-chamber modeling were used.

Results and discussion. The pharmacokinetic data showed a linear nature of pharmacokinetics of the drug based on LOAP as the foundation of data of the lithium’s amount in the blood plasma of rabbits after intragastric administration at doses of 200, 400 and 800 mg/kg. The drug with intragastric administration at a dose of 800 mg/kg is well absorbed from the gastrointestinal tract, with bioavailability (F) 74 %. This dose shows the maximum increase of the area under the pharmacokinetic curve (AUC - 32787.1 (ng x h)/ ml), and indicators of elimination constant (Kel - 0.062 h-1), clearance (Cl - 0.09 l/(kg x h)), elimination half-life (T1/2p - 11.436 h) in comparison with other doses remain unchanged.

About the Authors

M. A. Korolev
Research Institute of Clinical and Experimental Lymphology - Branch of Federal Research Center Institute of Cytology and Genetics, SB RAS
Russian Federation

Maksim Aleksandrovich Korolev - candidate of medical sciences.

630060, Novosibirsk, Timakov str., 2



V. I. Konenkov
Research Institute of Clinical and Experimental Lymphology - Branch of Federal Research Center Institute of Cytology and Genetics, SB RAS
Russian Federation

Vladimir Iosifovich Konenkov - doctor of medical sciences, professor, academician of the RAS.

630060, Novosibirsk, Timakov str., 2



L. N. Rachkovskaya
Research Institute of Clinical and Experimental Lymphology - Branch of Federal Research Center Institute of Cytology and Genetics, SB RAS
Russian Federation

Lyubov Nikiforovna Rachkovskaya - candidate of chemical sciences.

630060, Novosibirsk, Timakov str., 2



K. I. Ershov
Novosibirsk State Medical University of Minzdrav of Russia
Russian Federation

Konstantin Igorevich Ershov

630091, Novosibirsk, Krasny av., 52



G. I. Baykalov
Research Institute of Clinical and Experimental Lymphology - Branch of Federal Research Center Institute of Cytology and Genetics, SB RAS; Novosibirsk State Medical University of Minzdrav of Russia
Russian Federation

German Igorevich Baykalov

630060, Novosibirsk, Timakov str., 2; 630091, Novosibirsk, Krasny av., 52


N. E. Baykalova
Research Institute of Clinical and Experimental Lymphology - Branch of Federal Research Center Institute of Cytology and Genetics, SB RAS; Novosibirsk State Medical University of Minzdrav of Russia
Russian Federation

Natalya Evgen’evna Baykalova

630060, Novosibirsk, Timakov str., 2; 630091, Novosibirsk, Krasny av., 52



K. I. Bakhareva
Research Institute of Clinical and Experimental Lymphology - Branch of Federal Research Center Institute of Cytology and Genetics, SB RAS
Russian Federation

Kseniya Igorevna Bakhareva

630060, Novosibirsk, Timakov str., 2



P. G. Madonov
Research Institute of Clinical and Experimental Lymphology - Branch of Federal Research Center Institute of Cytology and Genetics, SB RAS; Novosibirsk State Medical University of Minzdrav of Russia
Russian Federation

Pavel Gennad’evich Madonov - doctor of medical sciences.

630060, Novosibirsk, Timakov str., 2; 630091, Novosibirsk, Krasny av., 52



References

1. Borodin Yu.I., Robinson M.V., Dameva I.S., Ra-chkovskaya L.N., Korolev M.A., Letyagin A.Yu. Lithium compounds in biology and medicine. Novosibirsk: Azart, 2016. 50 p. [In Russian].

2. Karkishchenko N.N., Khoronko V.V., Sergeeva S.A., Karkishchenko V.N. Pharmacokinetics. Rostov-on-Don, 2001. p. 383. [In Russian].

3. Lakin G.F. Biometrics. Moscow: Vysshaya shkola, 1990. 352 p. [In Russian].

4. Miroshnichenko I.I. Fundamentals of pharmacokinetics. Moscow: GEOTAR-Media, 2002. 188 p. [In Russian].

5. Ostrenko K.S., Koloskova E.M. The antidepressant effect of lithium ascorbate in experimental model of stress in rats. Vestnik nauki i obrazovaniya = Bulletin of Science and Education. 2016; (1): 19-21. [In Russian].

6. Ostrenko K.S., Rastashansky V.V The effect of various doses of the composition of lithium ascorbate, pyridoxine hydrochloride and thiamine mononitrate on neuropsychic excitation and adaptive activity in rats. Nauka i mir = Science and World. 2016; (1): 104-105. [In Russian].

7. Piotrovsky V.K. The method of statistical moments and integral model-independent parameters of pharmacokinetics. Farmakologiya i toksikologiya = Pharmacology and Toxicology. 1986; (5): 118-125. [In Russian].

8. Pronin A.V., Gromova O.A., Torshin I.Yu., Volkov A.Yu., Gogoleva I.V., Zhidomorov N.Yu. Investigation of the pharmacokinetics and compartmentaliza-tion of lithium ascorbate. Molodoy uchenyy = Young Scientist. 2016; (15): 547-555. [In Russian].

9. Guideline for preclinical studies of drugs. Part One. Ed. A.N. Mironov. Moscow: Grif i K, 2012. 944 p. [In Russian].

10. Socially significant diseases of the Russian population in 2018 (Statistical materials), Moscow, 2019. 37. [In Russian].

11. Ahmed I., Manno F.A.M., Manno S.H.C., Liu Y., Zhang Y., Lau C. Detection of lithium in breast milk and in situ elemental analysis of the mammary gland. Biomed. Opt. Express. 2018; 9 (9): 4184-4195. doi: 10.1364/BOE.9.004184

12. Ahmed I., Yang J., Law A.W.L., Manno F.A.M., Ahmed R., Zhang Y., Lau C. Rapid and in situ optical detection of trace lithium in tissues. Biomed. Opt. Express. 2018; 9 (9): 4459-4471. doi: 10.1364/BOE.9.004459

13. El-Balkhi S., Megarbane B., Poupon J., Baud F.J., Galliot-Guilley M. Lithium poisoning: is determination of the red blood cell lithium concentration useful? Clin. Toxicol. (Phila.). 2009; 47 (1): 8-13.

14. Ge W., Jakobsson E. Systems biology understanding of the effects of lithium on affective and neurodegenerative disorders. Front. Neurosci. 2018; 12: 933. doi: 10.3389/fnins.2018.00933

15. Kandil E., Dackiw A.P., Alabbas H., Abdullah O., Tufaro A.P., Tufano R.P. A profile of patients with hyperparathyroidism undergoing lithium therapy for affective psychiatric disorders. Head Neck. 2011; 33 (7): 925-927.

16. Malhi G.S., Tanious M., Das P., Berk M. The science and practice of lithium therapy. Aust. N. Z. J. Psychiatry. 2012. 46: 192-211.

17. Muller-Oerlinghausen B., Lewitzka U. Lithium reduces pathological aggression and suicidality: a minireview. Neuropsychobiology. 2010; 62 (1): 43-49. doi: 10.1159/000314309

18. Post R.M. The new news about lithium: An underutilized treatment in the United States. Neuropsychopharmacology. 2018; 43 (5): 1174-1179. doi: 10.1038/npp.2017.238

19. Qassem M., Triantis I., Hickey M., Palazidou E., Kyriacou P. Methodology for rapid assessment of blood lithium levels in ultramicro volumes of blood plasma for applications in personal monitoring of patients with bipolar mood disorder. J. Biomed. Opt. 2018; 23 (10): 1-6. doi: 10.1117/1JBO.23.10.107004

20. Saeidnia S., Abdollahi M. Concerns on the growing use of lithium: the pros and cons. Iran Red. Crescent. Med. J. 2013; 15 (8): 629-632. doi: 10.5812/ircmj.13756


Review

For citations:


Korolev M.A., Konenkov V.I., Rachkovskaya L.N., Ershov K.I., Baykalov G.I., Baykalova N.E., Bakhareva K.I., Madonov P.G. Studying the pharmacokinetic parameters of new normothymic drug based on the complex of lithium citrate, aluminum oxide and polymethylsiloxane. Сибирский научный медицинский журнал. 2019;39(6):14-21. (In Russ.) https://doi.org/10.15372/SSMJ20190602

Views: 440


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2410-2512 (Print)
ISSN 2410-2520 (Online)