STUDYING THE PHARMACOKINETIC PARAMETERS OF NEW NORMOTHYMIC DRUG BASED ON THE COMPLEX OF LITHIUM CITRATE, ALUMINUM OXIDE AND POLYMETHYLSILOXANE
Maksim Aleksandrovich KOROLEV1, Vladimir Iosifovich KONENKOV1, Lyubov Nikiforovna RACHKOVSKAYA1, Konstantin Igorevich ERSHOV2, German Igorevich BAYKALOV1,3, Natalya Evgen’evna BAYKALOVA1,3, Kseniya Igorevna BAKHAREVA1, Pavel Gennad’evich MADONOV1,3
1Research Institute of
Clinical and Experimental Lymphology - Branch of Federal Research Center
Institute of Cytology and Genetics of SB RAS
2Novosibirsk State Medical University of Minzdrav of Russia
3Novosibirsk State Medical
University of Minzdrav of Russia
Keywords: нормотимик, цитрат лития, оксид алюминия, полиметилсилоксан, фармакокинетика, normotymic, lithium citrate, aluminum oxide, polymethylsiloxane, pharmacokinetics
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 × h)/ml),
and indicators of elimination constant (Kel - 0.062 h-1), clearance (Сl - 0.09 l/(kg × h)), elimination half-life (T1/2β - 11.436 h) in comparison with other doses remain unchanged.
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