ABSTRACT
Aim To investigate the effects of different species Fc receptors (FcRn) on pharmacokinetic characteristics of MIL94, a monoclonal antibody against West Nile virus developed by Academy of Military Sciences, which has a neutralizing effect on West Nile virus and whose maintenance time in vivo is closely related to its antiviral effect. Methods The pharmacokinetic characteristics of MIL94 in mice expressing FcRn of different species (wild-type mice, hFcRn mice and FcRn knockout mice) were compared-. Wild-type mice and FcRn knockout mice were injected intravenously with MIL94 respectively. HFcRn mice were randomly divided into four groups. Two groups were injected intravenously with MIL94, and the other two groups were injected intravenously with intravenous immunoglobulin (IVIG) and then intravenously with MIL94. Indirect ELISA was used to determine the MIL94 concentration in mouse serum. WinNonlin software was used to calculate the pharmacokinetic parameters. Results After intravenous injection with MIL94, the in vivo pharmacokinetics were basically linear. The distribution volume of MIL94 in animals was related to FcRn. The half-life in vivo varied greatly between different groups. Conclusions FcRn can affect the half-life of MIL94 in different species mainly via alternation of its elimination and distribution. It is expected that the half-life of FcRn in human will be longer than that in preclinical animals.
ABSTRACT
Aim To investigate the effects of YL- IPA08 on the endogenous metabolites of PTSD model rats by metabolomics methods, and to explore the metabolic pathways and possible mechanisms of YL-IPA08 against PTSD. Methods The rats were randomly divided into control group, PTSD model group, and administration group of PTSD rats induced by forced swimming test, and the treatment group was given YL- IPA08 (2 mg • kg"1) by intragastric gavage for 15 consecutive days. High-performance liquid chromatog- raphy-mass spectrometry (HPLC-MS/MS) technology was used to detect the endogenous differential metabolites and the associated metabolic pathways in rat plasma samples. Targeted quantitative technology was simultaneously applied to detect the concentrations of 18 bile acids in rat plasma. Results Compared with control group, 40 kinds of endogenous metabolites including glutamic acid, proline, valine, arginine, leucine , cholic acid, and creatine showed significant difference, and the concentrations of 11 bile acids significantly increased in plasma of model group as well. Compared with model group, after YL-IPA08 intervention , the above-mentioned potential metabolites ap-peared to return to normal levels. Conclusions Metabolomics analysis reveals that YL-IPA08 has intervention effect on PTSD model rats. The mechanism may be related to the regulation of amino acid metabolism and bile acid metabolism.