Prediction of pharmacokinetic profiles of ampicillin sodium, gentamicin sulfate, and combination ampicillin sodium-gentamicin sulfate in serum and synovia of healthy horses.
Abstract: Pharmacokinetics of ampicillin sodium (11 mg/kg), gentamicin sulfate (2.2 mg/kg), and combination ampicillin sodium-gentamicin sulfate were determined for serum and synovia of healthy horses given single-dose IV injection and were not found to be different from those from other reports; however, a prolonged terminal gamma-phase for gentamicin (8,498 +/- 1,842 minutes) in serum of horses was found to exist. Pharmacokinetic interaction between combination ampicillin sodium-gentamicin sulfate was not observed int he serum or synovia. Prediction of ampicillin sodium or gentamicin sulfate concentrations in synovia, based on serum-based pharmacokinetics, cannot be accomplished solely upon analysis of peripheral-compartment pharmacokinetics. However, once equilibrium is achieved between synovia and extracellular fluid in the peripheral compartment, the decrease in drug concentrations in synovia parallels that in serum. Therefore, after 6 hours, synovial concentrations of gentamicin sulfate can be predicted based on peripheral-compartment pharmacokinetics, using an appropriate correction factor. The significance of these findings need to be correlated with clinical conditions so that a pharmacostatistical model for the prediction of synovial concentrations of drug(s) during treatment of horses with septic arthritis can be developed.
Publication Date: 1986-07-01 PubMed ID: 3740631
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- Journal Article
- Research Support
- Non-U.S. Gov't
- Research Support
- U.S. Gov't
- P.H.S.
Summary
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This research examines the pharmacokinetics of ampicillin sodium and gentamicin sulfate, both individually and combined, in the serum and synovia of healthy horses. The study highlights complex interactions between these drugs and their serum and synovia concentrations, suggesting that predictions based solely on serum-based pharmacokinetics are insufficient.
Study Overview and Key Findings
- The research investigates the pharmacokinetics, which refers to the way drugs are absorbed, distributed, metabolised, and excreted from the body, of two antibiotics (ampicillin sodium and gentamicin sulfate). The researchers also consider their combination. Single doses of these drugs are administered to horses via intravenous injection.
- The results confirm no significant differences when compared to previous reports, but identify a prolonged terminal phase for gentamicin in horse serum. This means that gentamicin’s elimination from the serum of horses is slower than anticipated, taking longer than other phases of drug action.
- The researchers do not observe any pharmacokinetic interactions between the combined use of ampicillin sodium and gentamicin sulfate, implying that usage of one does not affect the actions of the other.
Implications for Drug Concentration Predictions
- Contrary to common practice, the study indicates that predicting drug concentrations in synovia (fluid-filled cavities in joints) based solely on serum-based pharmacokinetics is not reliable.
- It is found, however, that once a balance is reached between the synovia and the extracellular fluid in the peripheral compartment (body fluids located outside of the cells), the decline in drug concentrations in the synovia parallels that in the serum.
- Due to this finding, after 6 hours, the study suggests that synovial concentrations of gentamicin sulfate can potentially be predicted based on the pharmacokinetics of the peripheral compartment, albeit with an appropriate correction factor.
Future Research Directions
- The researchers highlight that the relevance of their findings need to be verified in conjunction with clinical conditions. Essentially, it’s necessary to correlate their results with real-world scenarios on administering these drugs to horses.
- The ultimate aim for such research is the creation of a pharmacostatistical model, which can effectively predict the concentrations of these antibiotics in the joint fluids of horses during treatment for septic arthritis, thereby optimising treatment protocols.
Cite This Article
APA
Bowman KF, Dix LP, Riond JL, Riviere JE.
(1986).
Prediction of pharmacokinetic profiles of ampicillin sodium, gentamicin sulfate, and combination ampicillin sodium-gentamicin sulfate in serum and synovia of healthy horses.
Am J Vet Res, 47(7), 1590-1596.
Publication
Researcher Affiliations
MeSH Terms
- Ampicillin / blood
- Ampicillin / metabolism
- Ampicillin / therapeutic use
- Animals
- Drug Interactions
- Drug Therapy, Combination
- Female
- Gentamicins / blood
- Gentamicins / metabolism
- Gentamicins / therapeutic use
- Horses
- Kinetics
- Synovial Fluid / metabolism
Grant Funding
- ES 07046 / NIEHS NIH HHS
Citations
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