Study of the plasma pharmacokinetics and faecal excretion of the prodrug olsalazine and its metabolites after oral administration to horses.
Abstract: Olsalazine sodium (Dipentum*) has been used therapeutically against inflammatory bowel disease in human medicine as an alternative to sulphasalazine over the past 20 years. Bacteria in the colon split this prodrug into two molecules of the locally effective 5-aminosalicylic acid (5-ASA). Considering the potential therapeutic use in equine colitis, the pharmacokinetics of olsalazine (OLZ) after single oral administration to six horses at a dosage of 30 mg/kg was investigated. Plasma concentrations of OLZ, 5-ASA, and its main metabolite N-acetyl-5-aminosalicylic acid (Ac-5-ASA) were analysed by high-performance liquid chromatography methods. Evaluation of the plasma pharmacokinetics revealed a rapid, but low extent of absorption of OLZ (peak concentrations around 1 microg/mL at 0.5-1.5 h), and a delayed minimal absorption of 5-ASA (concentrations < 0.2 microg/mL, at 11-35 h), which is immediately metabolized to Ac-5-ASA. As indicators of the local availability in the colon, high faecal water concentrations of 5-ASA and Ac-5-ASA (mean C(max) about 300 and 130 microg/mL, respectively), but only traces of OLZ were found in faeces excreted 18-50 h after dosing. Of the administered OLZ dose 26% could be recovered from faeces, almost completely as 5-ASA and Ac-5-ASA. Routine clinical examination of the horses and assay of standard haematological and serum chemistry parameters before and after OLZ administration confirmed that a single dosage of 30 mg/kg was well tolerated. To estimate the systemic availability of 5-ASA liberated from OLZ, 5-ASA was administered i.v. at a dosage of 1.5 mg/kg to four horses and plasma concentrations of 5-ASA and Ac-5-ASA were determined. The pharmacokinetic evaluation showed a very low bioavailability of 2.4% for 5-ASA, released from orally administered OLZ. Furthermore, in an in vitro experiment, the metabolic transformation of 5-ASA to Ac-5-ASA mediated by bacteria in the caecal content of horses was determined at 38 degrees C for 31 h and compared with the metabolism data of the in vivo study. The markedly lower degree of acetylation in vitro supports the assumption that biotransformation of 5-ASA in vivo occurs not only by colonic bacteria, but also at other sites.
Publication Date: 2002-05-10 PubMed ID: 12000534DOI: 10.1046/j.1365-2885.2002.00395.xGoogle Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research paper carries out an in-depth study on the drug, olsalazine sodium, and its interaction in the horse’s body. The paper investigates how the drug is broken down and eliminated from the body after being orally consumed.
Introduction
The study focuses on a drug called olsalazine sodium, which was used as an alternative to sulphasalazine to treat inflammatory bowel disease in humans. The researchers were interested in the potential therapeutic use of this drug in horses. Six horses were given a single dosage of this drug, and the pharmacokinetics, i.e., the drug’s movement within the body, was studied.
Procedure and Results
- The horses were given a dosage of 30 mg/kg of olsalazine.
- The concentrations of olsalazine, 5-aminosalicylic acid (a product of olsalazine), and its main metabolite N-acetyl-5-aminosalicylic acid (Ac-5-ASA) in the animals’ plasma were analyzed.
- The results revealed that absorption of olsalazine was rapid but in a small amount, and there was a delayed minimal absorption of 5-ASA that was instantly metabolized to Ac-5-ASA.
- Indications of the local availability of the drug in the colon were determined through high faecal water concentrations of 5-ASA and Ac-5-ASA, but only traces of olsalazine were found in the faeces.
- About 26% of the administered olsalazine dose could be recovered from the faeces, largely as 5-ASA and Ac-5-ASA.
Tolerance and Bioavailability
- The health parameters of the horses were monitored before and after the administration of olsalazine. The results confirmed that a single dosage of 30 mg/kg was well tolerated by the horses.
- The systemic availability of 5-ASA that is separated from olsalazine was studied by giving four horses a IV dosage of 1.5 mg/kg of 5-ASA and measuring plasma concentrations of 5-ASA and Ac-5-ASA.
- The pharmacokinetics evaluation revealed a low bioavailability of only 2.4% for 5-ASA when released from orally administered olsalazine.
Additional Findings
- An in-vitro experiment was performed to explore the metabolic transformation of 5-ASA to Ac-5-ASA using bacteria in the caecal content of horses.
- Comparisons with in-vivo metabolism data suggested that biotransformation of 5-ASA occurs not only by colonic bacteria but also at other sites.
The findings of the research may help in understanding how horses tolerate human drugs and how these drugs behave in the animal’s body.
Cite This Article
APA
Knoll U, Strauhs P, Schusser G, Ungemach FR.
(2002).
Study of the plasma pharmacokinetics and faecal excretion of the prodrug olsalazine and its metabolites after oral administration to horses.
J Vet Pharmacol Ther, 25(2), 135-143.
https://doi.org/10.1046/j.1365-2885.2002.00395.x Publication
Researcher Affiliations
- Institute of Pharmacology, Pharmacy und Toxicology, Faculty of Veterinary Medicine, University of Leipzig, An den Tierkliniken 15, Leipzig, Germany.
MeSH Terms
- Administration, Oral
- Aminosalicylic Acids / administration & dosage
- Aminosalicylic Acids / blood
- Aminosalicylic Acids / pharmacokinetics
- Animals
- Area Under Curve
- Chromatography, High Pressure Liquid / veterinary
- Feces / chemistry
- Female
- Horse Diseases / drug therapy
- Horses / metabolism
- Inflammatory Bowel Diseases / drug therapy
- Inflammatory Bowel Diseases / veterinary
- Infusions, Intravenous / veterinary
- Male
- Prodrugs / administration & dosage
- Prodrugs / pharmacokinetics
Citations
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