Pharmacokinetics and bioavailability of ticarcillin and clavulanate in foals after intravenous and intramuscular administration.
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 (beta) and clearance (ClB) for ticarcillin were significantly less (P less than 0.01), and volume of distribution at steady state (Vd(ss)) was significantly larger (P less than 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 less than 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 less than 0.01), and the elimination-rate constant (kd) for clavulanate was significantly less (P less than 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 micrograms/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 less than or equal to 16 micrograms/ml), it should be administered i.v. four times daily.
Publication Date: 1991-03-01 PubMed ID: 2038098DOI: 10.1111/j.1365-2885.1991.tb00807.xGoogle Scholar: Lookup
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- Comparative Study
- Journal Article
- Research Support
- Non-U.S. Gov't
- Research Support
- U.S. Gov't
- P.H.S.
Summary
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The research focuses on studying the pharmacokinetics (what the body does to the drug) and bioavailability (the extent and rate at which the drug or medicine is absorbed into a living system and becomes available at the site of physiological activity) of ticarcillin and clavulanate in young foals. It found that the drugs were more widely distributed and slowly eliminated in the bodies of 3-day-old foals compared to 28-day-old ones, likely due to immature kidney function in the younger animals.
Methodology and Findings
- The study administered a combination of ticarcillin disodium and clavulanate potassium to healthy foals intravenously (in the vein) and intramuscularly (in the muscles).
- The distribution and metabolism of these drugs in foals were best understood using a two-compartment open model, a mathematical model used in pharmacokinetics to describe the body’s processing of a drug.
- The findings showed that ticarcillin and clavulanate were eliminated at a significantly slower rate and more widely distributed in the body of 3-day-old foals compared to 28-day-old ones. The volume of distribution for ticarcillin was also observed to be significantly larger in younger foals.
Implications
- These differences in ticarcillin and clavulanate metabolism were attributed to immature renal excretion mechanisms in younger foals. In other words, the kidneys of newborn foals are not fully developed, affecting how they process drugs.
- After intramuscular administration, clavulanate concentrations peaked significantly later in the body of 3-day-old foals compared to 28-day-old ones.
- In terms of bioavailability, both ticarcillin and clavulanate reached 100% and 88.3% respectively in 3-day-old foals post intramuscular administration. Unfortunately, the bioavailability of clavulanate decreased dramatically in 28-day-old foals, indicating that age influences how these medications work in the body.
Recommendations
- Given these findings, the researchers recommend administering the ticarcillin and clavulanate combination intravenously. This method is used due to the frequency of administration, and the pain caused by intramuscular injection, which is more often in neonates, yet essential in treating infections caused by susceptible organisms.
Taking into consideration this study’s findings, the authors highlighted the importance of considering the age and development of the animal when determining the mode of administering drugs, as well as the dosing regimens.
Cite This Article
APA
Wilson WD, Spensley MS, Baggot JD, Hietala SK, Pryor P.
(1991).
Pharmacokinetics and bioavailability of ticarcillin and clavulanate in foals after intravenous and intramuscular administration.
J Vet Pharmacol Ther, 14(1), 78-89.
https://doi.org/10.1111/j.1365-2885.1991.tb00807.x Publication
Researcher Affiliations
- Department of Medicine, School of Veterinary Medicine, University of California, Davis 95616.
MeSH Terms
- Age Factors
- Animals
- Animals, Newborn / metabolism
- Biological Availability
- Clavulanic Acid
- Clavulanic Acids / administration & dosage
- Clavulanic Acids / pharmacokinetics
- Female
- Gram-Negative Bacteria / drug effects
- Gram-Positive Bacteria / drug effects
- Horses / metabolism
- Injections, Intramuscular / veterinary
- Injections, Intravenous / veterinary
- Male
- Metabolic Clearance Rate
- Ticarcillin / administration & dosage
- Ticarcillin / pharmacokinetics
Grant Funding
- 2S07RR05457 / NCRR NIH HHS
Citations
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