Pharmacokinetic-pharmacodynamic integration of marbofloxacin after single and repeated intravenous administration in goats. (December 2018)

• Record Type: Journal Article
• Authors: Bhardwaj, Pallavi; Sidhu, Pritam K.; Lonare, M.K.; Kaur, Rajdeep; Dumka, V.K.; Rampal, S.
• Is Part Of: Research in veterinary science. Volume 121(2018)
• Page Start: 111
• Page End: 115
• Publication Date: 2018-12
• Subjects: Goat -- Intravenous -- Marbofloxacin -- Pharmacokinetics -- PK/PD integration -- Repeated administration; Veterinary medicine -- Periodicals; Veterinary Medicine -- Periodicals; Médecine vétérinaire -- Périodiques; Médecine vétérinaire -- Recherche -- Périodiques; Diergeneeskunde; 636.089
• DOI: 10.1016/j.rvsc.2018.10.010
• Languages: English
• ISSNs: 0034-5288

Abstract

Abstract: The single dose pharmacokinetics (PK) of marbofloxacin was compared with repeated intravenous (IV) administrations in six healthy goats at the dose rate of 2 mg/kg body weight at 24 h interval for 5 days. Blood samples were collected at times: 5, 15, 30 min and 1, 2, 4, 6, 9, 12, 24, 36, 48 and 72 h post drug administration. Plasma drug concentrations were determined by High Performance Liquid Chromatography and concentration-time data were subjected to non-compartment analysis. The MIC and MBC of marbofloxacin against Escherichia (E.) coli and Pasteurella (P.) multocida in Mueller Hinton Broth were determined by broth microdilution method. The t1/2elm = 4.37 ± 0.18 h and ClB = 0.29 ± 0.01 following single administration were not significantly different from t1/2elm = 5.11 ± 0.22 h and ClB = 0.26 ± 0.01 mL/kg/h after repeated administrations of marbofloxacin. Accumulation index (AI = 1.1) indicated no accumulation of marbofloxacin following repeated IV administrations up to 5 days. The respective MICs of marbofloxacin against E. coli and P. multocida were 0.03 μg/mL and 0.4 μg/mL. The AUC0–24h /MIC ratios were 226.64 ± 7.21 h for E. coli and 16.99 ± 0.541 h for P. multocida . PK/PD integration indicated that marbofloxacin daily dose of 2 mg/kg is appropriate for treating E. coli (MIC ≤ 0.03 μg/mL) infections. However, a higher dose of 6 mg/kg/day is suggested to obtain clinical cure against diseases caused by P. multocida having MIC90 = 0.12 μg/mL in goat species. Highlights: Pharmacokinetics of marbofloxacin was not altered following single and repeated IV administrations in goats. The AUCs were 7.69 ± 0.26 µg/mL.h and 6.99 ± 0.17 µg/mL.h on 5th and 1st administration of marbofloxacin, respectively. No drug accumulation (AI=1.1) following repeated IV administrations up to 5 days was observed in goats. Marbofloxacin dosage of 2 mg/kg/24h was determined for treatment of E. coli (MIC ≤ 0.03 µg/mL) infections in goats. A revised dosage of 6 mg/kg/24h is indicated to obtain clinical cure against P. multocida (MIC90 = 0.12 µg/mL).