Simultaneous determination of multicomponent of acetylkitasamycin and kitasamycin by LC–MS/MS in swine plasma and its application in a pharmacokinetic study

Q4 · MEDICINE

Article

Author: Liu, Zhenli ; Tao, Yanfei ; Pan, Yuanhu ; Xie, Shuyu ; Chen, Dongmei ; Yuan, Zonghui ; Huang, Lingli ; Zhang, Heying ; Xi, Chenglong

AbstractA simple and reliable LC–MS/MS method was established for simultaneous determination of 12 components from acetylkitasamycin and kitasamycin in swine plasma. The analytes were separated on a Shim‐pack VP‐ODS column with a 25 min gradient elution using 5 mmol/L ammonium acetate and acetonitrile as the mobile phase at a flow rate of 0.2 mL/min. Identification and quantification were accomplished by electrospray ionization) in positive mode using multiple reaction monitoring. The limits of quantitation of acetylkitasamycin A1A3, A13 and kitasamycin A3, A13 were 3 μg/L, and that of the other eight components was 5 μg/L. The mean recoveries of kitasamycin and acetylkitasamycin ranged from 85.3 to 103.5%. The developed method was successfully applied to a pharmacokinetic study in swine after intravenous (i.v.) and oral (p.o.) administration of acetylkitasamycin. The result showed that the plasma concentrations of acetylkitsamycin components were much higher than that of kitasamycin in swine after i.v. and p.o., in which acetylkitsamycin A4A5 was the highest component at each time point.

01 Dec 2017·Journal of Veterinary Pharmacology and TherapeuticsQ3 · AGRICULTURAL & FORESTRY SCIENCE

Pharmacokinetic and pharmacodynamic integration and modeling of acetylkitasamycin in swine for Clostridium perfringens

Q3 · AGRICULTURAL & FORESTRY SCIENCE

Article

Author: Yuan, Z. ; Hao, H. ; Xie, S. ; Liu, Z. ; Huang, L. ; Nan, J. ; Mao, F. ; Xi, C. ; Pan, Y.

The aim of this study was to establish an integrated pharmacokinetic/pharmacodynamic (PK/PD) modeling approach of acetylkitasamycin for designing dosage regimens and decreasing the emergence of drug‐resistant bacteria. After oral administration of acetylkitasamycin to healthy and infected pigs at the dose of 50 mg/kg body weights (bw), a rapid and sensitive LC–MS/MS method was developed and validated for determining the concentration change of the major components of acetylkitasamycin and its possible metabolite kitasamycin in the intestinal samples taken from the T‐shape ileal cannula. The PK parameters, including the integrated peak concentration (Cmax), the time when the maximum concentration reached (Tmax) and the area under the concentration–time curve (AUC), were calculated by WinNonlin software. The minimum inhibitory concentration (MIC) of 60 C. perfringens strains was determined following CLSI guideline. The in vitro and ex vivo activities of acetylkitasamycin in intestinal tract against a pathogenic strain of C. perfringens type A (CPFK122995) were established by the killing curve. Our PK data showed that the integrated Cmax, Tmax, and AUC were 14.57–15.81 μg/ml, 0.78–2.52 hR, and 123.84–152.32 μg hr/ml, respectively. The PD data show that MIC50 and MIC90 of the 60 C. perfringens isolates were 3.85 and 26.45 μg/ml, respectively. The ex vivo growth inhibition data were fitted to the inhibitory sigmoid Emax equation to provide the values of AUC/MIC to produce bacteriostasis (4.84 hr), bactericidal activity (15.46 hr), and bacterial eradication (24.99 hr). A dosage regimen of 18.63 mg/kg bw every 12 hr could be sufficient in the prevention of C. perfringens infection. The therapeutic dosage regimen for C. perfringens infection was at the dose of 51.36 mg/kg bw every 12 hr for 3 days. In summary, the dosage regimen for the treatment of C. perfringens in pigs administered with acetylkitasamycin was designed using PK/PD integrate model. The designed dose regimen could to some extent decrease the risk for emergence of macrolide resistance.

01 Jan 1976·Biochimica et Biophysica Acta (BBA) - Nucleic Acids and Protein Synthesis

Mechanism of action of acetyl kidamycin

Article

Author: Iwao Umezawa ; Masaaki Okamoto ; Kanki Komiyama ; Hideo Takeshima

Acetyl kidamycin, an antitumor antibiotic, was strongly bound to DNA in vitro, consequently, the melting temperature of DNA was significantly increased, and its buoyant density was decreased. From these results, it was suggested that acetyl kidamycin stabilized residual links between complementary strands by binding to DNA. An additional action was observed in that acetyl kidamycin caused single-strand scission of DNA in an alkaline sucrose density gradient solution.

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Bacterial Infections	CN	Chongqing Daxin Pharmaceutical Co. Ltd.	-

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