4.4 Article

Pharmacokinetics of a New Parenteral Formulation of Tilmicosin-La in Cows

期刊

PAKISTAN VETERINARY JOURNAL
卷 36, 期 2, 页码 165-168

出版社

UNIV AGRICULTURE, FAC VETERINARY SCIENCE

关键词

Cow; Long-acting; New-preparation; Pharmacokinetics; Tilmicosin

资金

  1. DGAPA-UNAM Program of Post-Doctoral Scholarships in the UNAM
  2. PROINNOVA/CONACYT in Mexico

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The blood serum pharmacokinetics of a Poloxamer-407 based new pharmaceutical preparation of 39% tilmicosin was determined in cows. Two dose levels injected SC, were assessed: 10 mg/kg (Til-LA(10)) and 26 mg/kg (Til-LA(26)). Tilmicosin was determined using HPLC, also electrocardiographic (EKG) monitoring in all animals before and at 1, 2 and 4 h after the injection of the drug was performed to measure key EKG parameters, including heart rate. Maximum serum concentration values were 2.6 mu g/mL and 1.23 mu g/mL, occurring 4.9 and 5.1 h after the injection of TilL-LA(26) and Til-LA10, respectively. Mean residence time was statistically larger for Til-LA(26) (50.4 +/- 5.8 h) than Til-LA10 (37.4 +/- 4.7 h) (P<0.05), with T-1/2el of 39.8 h for Til-LA(26) and 33.2 h for Til-LA10. There were no differences in relative bioavailability as adjusted for dose (AUMC of 8663 mu g/mLzh(2) for Til-LA(26) and 2858 mu g/mLzh(2) for Til-LA10). This new formulation as dosed for Til-LA(26) possesses a long T-1/2el of tilmicosin and resulted in a lack of changes in the EKG and heart rate. Based on PK/PD ratios tilmicosin is regarded as a time-dependent antibacterial drug. Considering a theoretical minimum therapeutic serum concentration (MTC) of 0.1 mu g/mL useful concentrations can be achieved for up to 192 h with Til-LA(26) and an AUC/MTC ratio of 1514 without cardiac toxicity. Further studies are necessary to correlate PK/PD parameters obtained with clinical efficacy and a more thorough analysis of cardiac toxicity is required to determine the suitability of this preparation in bovine medicine. (C) 2015 PVJ. All rights reserved

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