Regional intravenous limb perfusion compared to systemic intravenous administration for marimastat delivery to equine lamellar tissue

Underwood, C., Collins, S. N., Mills, P. C., Van Eps, A. W., Allavena, R. E., Medina Torres, C. E. and Pollitt, C. C. (2015) Regional intravenous limb perfusion compared to systemic intravenous administration for marimastat delivery to equine lamellar tissue. Journal of Veterinary Pharmacology and Therapeutics, 38 4: 392-399. doi:10.1111/jvp.12198


Author Underwood, C.
Collins, S. N.
Mills, P. C.
Van Eps, A. W.
Allavena, R. E.
Medina Torres, C. E.
Pollitt, C. C.
Title Regional intravenous limb perfusion compared to systemic intravenous administration for marimastat delivery to equine lamellar tissue
Journal name Journal of Veterinary Pharmacology and Therapeutics   Check publisher's open access policy
ISSN 1365-2885
0140-7783
Publication date 2015-08
Sub-type Article (original research)
DOI 10.1111/jvp.12198
Open Access Status
Volume 38
Issue 4
Start page 392
End page 399
Total pages 8
Place of publication Oxford, United Kingdom
Publisher Blackwell Publishing
Collection year 2016
Language eng
Formatted abstract
Pharmaceutical agents with potential for laminitis prevention have been identified. Many of these, including the MMP inhibitor marimastat, are impractical for systemic administration. This study compared local delivery of marimastat by regional limb perfusion (RLP) to systemic intravenous bolus dosing (SIVB), and established whether RLP results in local lamellar drug delivery. Six adult horses received 0.23 mg/kg of marimastat by RLP followed by 0.23 mg/kg marimastat by SIVB, with a 24-h washout period. Lamellar ultrafiltration probes sampled lamellar interstitial fluid as lamellar ultrafiltrate (LUF). LUF and plasma marimastat concentrations (LUF[M] and P[M], respectively) were measured for 24 h after each treatment. Regional pharmacokinetic parameters were calculated using noncompartmental analyses. The LUF Cmax following RLP was 232 [34–457] times that following SIVB. LUF[M] after RLP were higher than those obtained after SIVB for 18 h (P < 0.03). Median LUF[M] were > IC90 of equine lamellar MMP-2 and MMP-9 for 9 h after tourniquet removal. RLP appeared superior to SIVB for lamellar marimastat delivery (higher LUF Cmax,, AUC and T > IC90 of lamellar MMPs). However, frequent dosing is necessary to achieve therapeutic lamellar concentrations. RLP could be used to investigate whether marimastat prevents experimentally induced laminitis. Further refinement of the technique and dosing interval is necessary before clinical application.
Keyword Enquine
Laminitis prevention
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Veterinary Science Publications
 
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