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Home / Equine Research Bank / J Vet Pharmacol Ther / Pharmacodynamics and pharmacokinetics of nonsteroidal anti-i...
Journal of veterinary pharmacology and therapeutics2004; 27(6); 479-490; doi: 10.1111/j.1365-2885.2004.00617.x

Pharmacodynamics and pharmacokinetics of nonsteroidal anti-inflammatory drugs in species of veterinary interest.

Abstract: This review summarises selected aspects of the pharmacokinetics (PK) and pharmacodynamics (PD) of nonsteroidal anti-inflammatory drugs (NSAIDs). It is not intended to be comprehensive, in that it covers neither minor species nor several important aspects of NSAID PD. The limited objective of the review is to summarise those aspects of NSAID PK and PD, which are important to an understanding of PK-PD integration and PK-PD modelling (the subject of the next review in this issue). The general features of NSAID PK are: usually good bioavailability from oral, intramuscular and subcutaneous administration routes (but with delayed absorption in horses and ruminants after oral dosing), a high degree of binding to plasma protein, low volumes of distribution, limited excretion of administered dose as parent drug in urine, marked inter-species differences in clearance and elimination half-life and ready penetration into and slow clearance from acute inflammatory exudate. The therapeutic effects of NSAIDs are exerted both locally (at peripheral inflammatory sites) and centrally. There is widespread acceptance that the principal mechanism of action (both PD and toxicodynamics) of NSAIDs at the molecular level comprises inhibition of cyclooxygenase (COX), an enzyme in the arachidonic acid cascade, which generates inflammatory mediators of the prostaglandin group. However, NSAIDs possess also many other actions at the molecular level. Two isoforms of COX have been identified. Inhibition of COX-1 is likely to account for most of the side-effects of NSAIDs (gastrointestinal irritation, renotoxicity and inhibition of blood clotting) but a minor contribution also to some of the therapeutic effects (analgesic and anti-inflammatory actions) cannot be excluded. Inhibition of COX-2 accounts for most and possibly all of the therapeutic effects of NSAIDs. Consequently, there has been an intensive search to identify and develop drugs with selectivity for inhibition of COX-2. Whole blood in vitro assays are used to investigate quantitatively the three key PD parameters (efficacy, potency and sensitivity) for NSAID inhibition of COX isoforms, providing data on COX-1:COX-2 inhibition ratios. Limited published data point to species differences in NSAID-induced COX inhibition, for both potency and potency ratios. Members of the 2-arylpropionate sub-groups of NSAIDs exist in two enantiomeric forms [R-(-) and S-(+)] and are licensed as racemic mixtures. For these drugs there are marked enantiomeric differences in PK and PD properties of individual drugs in a given species, as well as important species differences in both PK and PD properties.
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Publication Date: 2004-12-17 PubMed ID: 15601442DOI: 10.1111/j.1365-2885.2004.00617.xGoogle Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research paper is a review that summarises the pharmacokinetics and pharmacodynamics aspects of nonsteroidal anti-inflammatory drugs (NSAIDs) in veterinary species, highlighting the general features of their absorption, action mechanisms, effects, and inter-species differences.

Pharmacokinetics of NSAIDs

This part of the review discusses the movement of NSAIDs within the body of different animal species. Key aspects included are:

  • Good bioavailability: These drugs can effectively enter the body’s system from oral, intramuscular and subcutaneous administration routes, although the absorption rate is delayed in horses and ruminants after oral dosing.
  • High degree of binding to plasma protein: means that a large proportion of the anti-inflammatory drugs have the ability to combine with proteins within the blood.
  • Low volumes of distribution: The NSAIDs do not spread widely within the body.
  • Limited excretion as parent drug: A small percentage of administered NSAIDs are excreted from the body without being metabolised.
  • Inter-species differences: The rates of clearance and elimination half-life of NSAIDs vary between different animal species.

Pharmacodynamics of NSAIDs

The paper further explores how NSAIDs affect the bodies of different animal species.

  • Mode of action: NSAIDs inhibit cyclooxygenase (COX), an enzyme that catalyses the production of prostaglandins which are mediators of inflammation. Besides, they also display other various actions at the molecular level.
  • Impact of COX inhibition: The inhibition of COX-1, one of the COX’s isoforms, primarily results in side effects such as gastrointestinal irritation, kidney toxicity and inhibition of blood clotting. Yet, it also contributes to some beneficial therapeutic effects. On the other hand, inhibiting COX-2, the other isoform, accounts for most, if not all, of the therapeutic effects of NSAIDs.
  • Differences across species: There are differences in NSAID-induced COX inhibition in terms of effectiveness and potency ratios across different species.

Focus on 2-arylpropionate family of NSAIDs

Special attention is given to the 2-arylpropionate subtype of NSAIDs that exists in two forms – R-(-) and S-(+).

  • PK and PD differences: There are species-specific differences and enantiomeric, or structural, differences in how the body processes these drugs (pharmacokinetics) and how they affect the body (pharmacodynamics).

Cite This Article

APA
Lees P, Landoni MF, Giraudel J, Toutain PL. (2004). Pharmacodynamics and pharmacokinetics of nonsteroidal anti-inflammatory drugs in species of veterinary interest. J Vet Pharmacol Ther, 27(6), 479-490. https://doi.org/10.1111/j.1365-2885.2004.00617.x

Publication

Journal of veterinary pharmacology and therapeutics
ISSN: 0140-7783
NlmUniqueID: 7910920
Country: England
Language: English
Volume: 27
Issue: 6
Pages: 479-490

Researcher Affiliations

Lees, P
  • Royal Veterinary College, Hawkshead Campus, Hatfield, Hertfordshire AL9 7TA, UK. plees@rvc.ac.uk
Landoni, M F
    Giraudel, J
      Toutain, P L

        MeSH Terms

        • Animals
        • Anti-Inflammatory Agents, Non-Steroidal / pharmacokinetics
        • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
        • Cyclooxygenase Inhibitors / pharmacokinetics
        • Cyclooxygenase Inhibitors / pharmacology
        • Humans
        • Inhibitory Concentration 50
        • Models, Animal
        • Models, Biological
        • Species Specificity
        • Veterinary Drugs / pharmacokinetics
        • Veterinary Drugs / pharmacology

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