ABSTRACT
COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.
ABSTRACT
Recently, more and more attentions of drug development are placed to macromolecules, such as monoclonal antibodies, proteins, etc. It has become one of the most promising areas in drug research and development in 21st Century. In terms of the structure and the ADMET (absorption, distribution, metabolism, excretion and toxicity), macromolecules is different from small molecule drugs, which lead to a distinct modeling strategy. The characterization of biologics ADMET processes and its application in the PK model selection of macromolecules are reviewed in this paper.
ABSTRACT
The aim of this paper is to develop and validate a rapid and sensitive LC-APCI/MS method for the determination of triptolide (TP) in plasma and to study the pharmacokinetic properties of TP in Beagle dogs. Sample preparation consisted of liquid-liquid extraction of interests. with ethyl acetate from dog plasma. The analytes and internal standard prednisolone were well separated on a Zorbax Extend-C18 analytical column. Plasma TP was detected by selected-ion monitoring (SIM) of LC-APCI/MS as its deprotonated molecular ions [M - H] - at m/z 358.9. Pharmacokinetic studies were undertaken in dogs following an iv dose of 0.05 mg x kg(-1) of TP or an ig dose of 0.05, 0.08, 0.1 mg x kg(-1), separately. The pharmacokinetic parameters were calculated by DAS software. Calibration curves were linear over the concentration range of 1 - 200 ng x mL(-1) of TP with the within- and between-batch precisions less than 10%. The within and between-batch accuracy was 95.0% to 105.0%. Recovery of LC-MS method for TP in plasma was over 75%. The T1/2beta was (2.5 +/- 0.8) h after intravenous administration of TP at the dose of 0.05 mg x kg(-1). There were no significant differences in T(max), T1/2 alpha and T1/2 beta among the three ig dosage groups. AUC and C(max) increased proportionally with doses. The absolute bioavailability of TP after ig administration of 0.05 mg x kg(-1) was (75 +/- 17)%. The LC-MS method for determination of triptolide in dog plasma was sensitive and rapid. It was showed that the elimination of triptolide was rapid. The absolute bioavailability of triptolide given orally was high.
Subject(s)
Animals , Dogs , Female , Male , Administration, Oral , Area Under Curve , Biological Availability , Chromatography, High Pressure Liquid , Diterpenes , Blood , Pharmacokinetics , Dose-Response Relationship, Drug , Epoxy Compounds , Blood , Pharmacokinetics , Injections, Intravenous , Mass Spectrometry , Phenanthrenes , Blood , Pharmacokinetics , Plants, Medicinal , Chemistry , Random Allocation , Tripterygium , ChemistryABSTRACT
To study the enzyme kinetics of schizandrin metabolism in different gender in rat liver microsomes, liver microsomes were prepared from male or female rats. Schizandrin was incubated with rat liver microsomes. Schizandrin and its metabolites were isolated and identified by HPLC-UV method. Vmax, Km and Cl(int) of schizandrin in male and female rat liver microsomes were (21.88 +/- 2.30) and (0.61 +/- 0.07) micromol x L(-1) x min(-1) x mg(-1) (protein), (389.00 +/- 46.26) and (72.64 +/- 13.61) micromol x L(-1), (0.0563 +/- 0.0007) and (0.0084 +/- 0.0008) min x mg(-1) (protein), respectively. The major metabolites of schizandrin in female and male rat liver microsomes were 7,8-dihydroxy-schizandrin (M1) and 7, 8-dihydroxy-2-demethyl schizandrin (M2b), respectively. Ketoconazole, quinidine, and orphenadrine had different level effects on schizandrin metabolism in both male and female rat liver microsomes, and cimetidine still had some inhibitory effect in male liver microsomes. CYP3A and CYP2C11 may be the main P450 enzymes in schizandrin metabolism and their difference in rat liver microsomes may be the main reason for the sex difference of metabolic enzyme kinetics and metabolites of schizandrin in rats.