Pharmacokinetics and tissue fluid distribution of cephalexin in the horse after oral and i.v. administration.
Abstract: The purpose of this study was to determine the pharmacokinetics and tissue fluid distribution of cephalexin in the adult horse following oral and i.v. administration. Cephalexin hydrate (10 mg/kg) was administered to horses i.v. and plasma samples were collected. Following a washout period, cephalexin (30 mg/kg) was administered intragastrically. Plasma, interstitial fluid (ISF) aqueous humor, and urine samples were collected. All samples were analyzed by high-pressure liquid chromatography (HPLC). Following i.v. administration, cephalexin had a plasma half-life (t(1/2)) of 2.02 h and volume of distribution [V(d(ss))] of 0.25 L/kg. Following oral administration, the average maximum plasma concentration (C(max)) was 3.47 mug/mL and an apparent half-life (t(1/2)) of 1.64 h. Bioavailability was approximately 5.0%. The AUC(ISF):AUC(plasma) ratio was 80.55% which corresponded to the percentage protein-unbound drug in the plasma (77.07%). The t(1/2) in the ISF was 2.49 h. Cephalexin was not detected in the aqueous humor. The octanol:water partition coefficient was 0.076 +/- 0.025. Cephalexin was concentrated in the urine with an average concentration of 47.59 microg/mL. No adverse events were noted during this study. This study showed that cephalexin at a dose of 30 mg/kg administered orally at 8 h dosage intervals in horses can produce plasma and interstitial fluid drug concentrations that are in a range recommended to treat susceptible gram-positive bacteria (MIC < or = 0.5 microg/mL). Because of the low oral bioavailability of cephalexin in the horse, the effect of chronic dosing on the normal intestinal bacterial flora requires further investigation.
Publication Date: 2005-10-07 PubMed ID: 16207304DOI: 10.1111/j.1365-2885.2005.00683.xGoogle Scholar: Lookup
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Summary
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The abstract summarizes a research study which aimed to understand how the drug cephalexin interacts within the bodies of adult horses, specifically studying how the drug moves and settles in the body after it is administered orally or through an injection (i.v.).
Objective of the Study
- The research was designed to determine the pharmacokinetics (the body’s effect on a drug), and tissue fluid distribution (where in body fluid the drug is distributed) of cephalexin in adult horses, after different methods of administration – oral and intravenous (i.v.).
Methodology
- A defined amount of cephalexin hydrate was administered to horses through injection, after which plasma samples were collected.
- Post this, a washout period was maintained, after which a different amount of cephalexin was administered orally. After this process, plasma, interstitial fluid (ISF) aqueous humor, and urine samples were collected.
- All collected samples were then analyzed through High-Pressure Liquid Chromatography (HPLC).
Findings
- The research found that after i.v. administration, the cephalexin had a half-life (time taken for the body to eliminate half of the drug) of 2.02 hours and a volume of distribution of 0.25 L/kg.
- Post oral administration, the maximum average concentration in plasma was found to be 3.47 microgram/mL with a half-life of 1.64 hours. The oral bioavailability (the extent and rate at which the drug enters the system) was roughly 5%.
- The ratio of Area Under the Curve (AUC) for interstitial fluid (ISF) to plasma was 80.55%, which corresponds to the percentage of the drug in the plasma that was not bound to protein (77.07%).
- Cephalexin was not detected in the aqueous humor (fluid in the eye), but was found concentrated in the urine, with an average concentration of 47.59 microgram/mL.
- No adverse events were observed during this study.
Conclusions and Further Research
- The study concluded that a dose of cephalexin, of 30 mg/kg given orally at 8-hour intervals can lead to plasma and interstitial fluid drug concentrations that are recommended for treating susceptible gram-positive bacteria in horses.
- However, due to the low oral bioavailability of cephalexin in horses, further research is needed to understand the effect of chronic dosing on the normal intestinal flora (the bacteria in the intestines).
Cite This Article
APA
Davis JL, Salmon JH, Papich MG.
(2005).
Pharmacokinetics and tissue fluid distribution of cephalexin in the horse after oral and i.v. administration.
J Vet Pharmacol Ther, 28(5), 425-431.
https://doi.org/10.1111/j.1365-2885.2005.00683.x Publication
Researcher Affiliations
- Clinical Pharmacology, Research Laboratories, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA. jennifer_davis@ncsu.edu
MeSH Terms
- Administration, Oral
- Animals
- Anti-Bacterial Agents / administration & dosage
- Anti-Bacterial Agents / blood
- Anti-Bacterial Agents / pharmacokinetics
- Area Under Curve
- Cephalexin / administration & dosage
- Cephalexin / blood
- Cephalexin / pharmacokinetics
- Cross-Over Studies
- Female
- Horses / metabolism
- Injections, Intravenous / veterinary
- Male
- Tissue Distribution
Citations
This article has been cited 3 times.- Heravi MM, Zadsirjan V. Prescribed drugs containing nitrogen heterocycles: an overview. RSC Adv 2020 Dec 9;10(72):44247-44311.
- Alborova A, Lademann J, Kramer A, Richter H, Patzelt A, Sterry W, Koch S. In vivo analysis of wound healing by optical methods. GMS Krankenhhyg Interdiszip 2008 Nov 3;3(1):Doc10.
- Sammeta SM, Vaka SR, Murthy SN. Dermal drug levels of antibiotic (cephalexin) determined by electroporation and transcutaneous sampling (ETS) technique. J Pharm Sci 2009 Aug;98(8):2677-85.
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