Effect of supportive therapy on the pharmacokinetics of intravenous marbofloxacin in endotoxemic sheep
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Tarih
2020
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Wiley
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
The purpose of this study was to determine the influences of supportive therapy (ST) on the pharmacokinetics (PK) of marbofloxacin in lipopolysaccharide (LPS)-induced endotoxemic sheep. Furthermore, minimum inhibitory concentration (MIC) of marbofloxacin against Escherichia coli, Mannheimia haemolytica, Pasteurella multocida, Klebsiella pneumoniae, Salmonella spp., and Staphylococcus aureus was determined. The study was performed using a three-period cross PK design following a 15-day washout period. In the first period, marbofloxacin (10 mg/kg) was administered by an intravenous (IV) injection. In the second and third periods, marbofloxacin was co-administered with ST (lactated ringer + 5% dextrose + 0.45% sodium chloride, IV, 20 ml/kg, dexamethasone 0.5 mg/kg, SC) and ST + LPS (E. coli O55:B5, 10 mu g/kg), respectively. Plasma marbofloxacin concentration was measured using HPLC-UV. Following IV administration of marbofloxacin alone, the t1/2 lambda z, AUC(0-infinity), Cl-T, and V-dss were 2.87 hr, 34.73 hr x mu g/ml, 0.29 L hr(-1) kg(-1), and 0.87 L/kg, respectively. While no change was found in the MBX + ST group in terms of the PK parameters of marbofloxacin, it was determined that the Cl-T of marbofloxacin decreased, AUC(0-infinity) increased, and t1/2 lambda z and MRT prolonged in the MBX + ST + LPS group. MIC values of marbofloxacin were 0.031 to >16 mu g/ml for E. coli, 0.016 to >16 mu g/ml for M. haemolytica, 0.016-1 mu g/ml for P. multocida, 0.016-0.25 mu g/ml for K. pneumoniae, 0.031-0.063 mu g/ml for Salmonella spp., and 0.031-1 mu g/ml for S. aureus. The study results show the necessity to make a dose adjustment of marbofloxacin following concomitant administration of ST in endotoxemic sheep. Also, the PK and pharmacodynamic effect of marbofloxacin needs to be determined in naturally infected septicemic sheep following concomitant administration of single and ST.
Açıklama
Anahtar Kelimeler
endotoxemia, marbofloxacin, pharmacokinetics, sheep, supportive therapy
Kaynak
Journal of Veterinary Pharmacology and Therapeutics
WoS Q Değeri
Q2
Scopus Q Değeri
Q1
Cilt
43
Sayı
3
