Pharmacokinetics and bioavailability of ticarcillin and clavulanate in foals after intravenous and intramuscular administration

William D Wilson, M. S. SPENSLEY, J. D. BAGGOT, S. K. HIETALA, P. PRYOR

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Abstract

The pharmacokinetics and bioavailability of ticarcillin and clavulanate were determined after intravenous (i.v.) or intramuscular (i.m.) administration of ticarcillin disodium (50 mg/kg) combined with clavulanate potassium (1.67 mg/kg) to groups of healthy foals at 3 days and 28 days of age. After i.v. administration of the combination to five foals, the disposition kinetics of ticarcillin and clavulanate were best described using a two‐compartment open model. Mean plasma elimination‐rate constant (ß) and clearance (Clb) for ticarcillin were significantly less (P < 0.01), and volume of distribution at steady state (Vd(ss)) was significantly larger (P < 0.05), in the foals at 3 days compared with 28 days of age. This indicated that renal excretion mechanisms were immature and ticarcillin was more widely distributed in 3‐day‐old foals. The mean elimination rate constant for clavulanate was significantly less (P < 0.01) at 3 days than at 28 days of age. Values of the major kinetic terms describing the disposition of ticarcillin after i.m. administration to five 3‐day‐old foals were not significantly different from values of these parameters in the same foals at 28 days of age. After i.m. administration of the drug combination, plasma clavulanate concentrations peaked significantly later (P<0.01), and the elimination‐rate constant (kd) for clavulanate was significantly less (P < 0.01), in 3‐day‐old foals than in 28‐day‐old foals. The bioavailabilities of ticarcillin and clavulanate after i.m. administration in 3‐day‐old foals were 100% and 88.3%, respectively, and in 28‐day‐old foals were 100% and 27.4%, respectively. Mean plasma ticarcillin concentrations exceeded 16 (μg/ml for a longer period after i.m. administration of the drug combination than after i.v. administration to foals of both age groups. By virtue of the frequency of administration required and the painful response elicited by i.m. injection, it is recommended that when the combination of ticarcillin disodium (50 mg/kg) and clavulanate potassium (1.67 mg/kg) is used in foals to treat infections caused by susceptible organisms (MIC ≤16 μ/ml), it should be administered i.v. four times daily.

Original languageEnglish (US)
Pages (from-to)78-89
Number of pages12
JournalJournal of Veterinary Pharmacology and Therapeutics
Volume14
Issue number1
DOIs
StatePublished - 1991

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ticarcillin
Ticarcillin
Clavulanic Acid
intramuscular injection
intravenous injection
foals
Intravenous Administration
Biological Availability
pharmacokinetics
bioavailability
Pharmacokinetics
Drug Combinations
combination drug therapy
Intramuscular Injections
potassium
kinetics
Age Groups

ASJC Scopus subject areas

  • Pharmacology
  • veterinary(all)

Cite this

Pharmacokinetics and bioavailability of ticarcillin and clavulanate in foals after intravenous and intramuscular administration. / Wilson, William D; SPENSLEY, M. S.; BAGGOT, J. D.; HIETALA, S. K.; PRYOR, P.

In: Journal of Veterinary Pharmacology and Therapeutics, Vol. 14, No. 1, 1991, p. 78-89.

Research output: Contribution to journalArticle

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N2 - The pharmacokinetics and bioavailability of ticarcillin and clavulanate were determined after intravenous (i.v.) or intramuscular (i.m.) administration of ticarcillin disodium (50 mg/kg) combined with clavulanate potassium (1.67 mg/kg) to groups of healthy foals at 3 days and 28 days of age. After i.v. administration of the combination to five foals, the disposition kinetics of ticarcillin and clavulanate were best described using a two‐compartment open model. Mean plasma elimination‐rate constant (ß) and clearance (Clb) for ticarcillin were significantly less (P < 0.01), and volume of distribution at steady state (Vd(ss)) was significantly larger (P < 0.05), in the foals at 3 days compared with 28 days of age. This indicated that renal excretion mechanisms were immature and ticarcillin was more widely distributed in 3‐day‐old foals. The mean elimination rate constant for clavulanate was significantly less (P < 0.01) at 3 days than at 28 days of age. Values of the major kinetic terms describing the disposition of ticarcillin after i.m. administration to five 3‐day‐old foals were not significantly different from values of these parameters in the same foals at 28 days of age. After i.m. administration of the drug combination, plasma clavulanate concentrations peaked significantly later (P<0.01), and the elimination‐rate constant (kd) for clavulanate was significantly less (P < 0.01), in 3‐day‐old foals than in 28‐day‐old foals. The bioavailabilities of ticarcillin and clavulanate after i.m. administration in 3‐day‐old foals were 100% and 88.3%, respectively, and in 28‐day‐old foals were 100% and 27.4%, respectively. Mean plasma ticarcillin concentrations exceeded 16 (μg/ml for a longer period after i.m. administration of the drug combination than after i.v. administration to foals of both age groups. By virtue of the frequency of administration required and the painful response elicited by i.m. injection, it is recommended that when the combination of ticarcillin disodium (50 mg/kg) and clavulanate potassium (1.67 mg/kg) is used in foals to treat infections caused by susceptible organisms (MIC ≤16 μ/ml), it should be administered i.v. four times daily.

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