Download Laminil Investigational Drug

PHARMACOLOGY DATA
LAMINIL
DESCRIPTION
Laminil is an intravenous mast cell stabilizer agent for aid in treatment of acute laminitis.
Formulation: Sterile powder in 5 gram vial (reconstitute sterile water for injection)
Dosage: Currently 5 grams per foot per injection
Administration: Retrograde venous therapy via injection into the digital vein below the
fetlock (using a tourniquet above the injection site).
Caution: Federal (U.S.) law restricts this drug to use by or on the order of a licensed
veterinarian.
Storage: Room temperature
CLINICAL PHARMACOLOGY
General: Laminil is a mast cell stabilizer. The drug inhibits the release of inflammatory
mediators from the cells involved in laminitic reactions. In in vitro studies with adult
humans, the drug has been shown to inhibit activation of and mediator release from a
variety of inflammatory cell types such as histamine, proteases, eosinophils, neutrophils,
macrophages, mast cells, monocytes and platelets and inhibit the release of additional
mediators such a leukotriene C4, prostaglandin D2 and various other cytokines. The drug
has anti-inflammatory properties. Laminil has shown promise in the treatment of acute
laminitis.
Mast cell stabilizers: Mast cell stabilizers include cromone medications typically used to
treat allergic disorders such as asthma, hay fever and allergic conjunctivitis. In general,
mast cell stabilizers act by blocking calcium channels essential for mast cell
degranulation and stabilizing the mast cell to prevent excess release of destructive
mediators such as histamine and proteases.
Antihistamines: Mast cell stabilizers are not antihistamines and, surprisingly and
unexpectedly, show more promise than antihistamines in the treatment of laminitis. Mast
cell stabilizers inhibit mast cell degranulation and the subsequent release of histamine and
metalloproteinases, while antihistamines attempt to block the action of histamine on a
target tissue. Mast cell stabilizers prevent localized and/or systemic release of histamine
and other mediators such as proteases in excess. Administration of a mast cell stabilizer
to treat laminitis appears to generate a uniform effect by acting upstream of histamine
release. Conversely, antihistamines attempt to block the action of histamine in a target
tissue, but fail to act directly on the release of histamine or to mitigate activity of other
mediators.
Antihistamines act directly on histamine released and thus can be overwhelmed by the
level of histamine in the blood. When histamine levels are high, it is difficult to
administer sufficient amounts of antihistamine to moderate the effects of histamine
without antihistamine-induced side effects. Unlike mast cell stabilizers, antihistamines
are subject to local concentration of histamine at any given release point and thus the
antihistamine can be underrepresented in some areas of the body or overrepresented in
others. Mast cell stabilizers administered at any given concentration will prevent
degranulation of mast cells, regardless of the location in the body. Mast cell stabilizers
are extremely effective in late-phase inflammatory reactions, while antihistamines have
no effect on late-phase reactions.
PHARMACOKINETICS
Bioavailability: Current practice is that the bioavailability of the drug is superior when
infused into the laminae of the foot. It is not metabolized and is primarily unchanged in
urine.
Route of delivery: The best route of delivery for the drug at the present is intravenously
using retrograde venous therapy. We tested other routes such as systemic intravenous
injection, oral, and topically with a patch, but at this date, retrograde venous therapy
shows superior efficacy.
Protein binding: The drug is approximately 89 percent protein bound in human plasma.
No data is available for horses, dairy calves or sheep.
Half-life: 24 hours or less
Drug Interaction: The drug, which is 89 percent protein binding, was concurrently used
with phenylbutazone (bute) and also banamine. Drug interaction took place with signs of
drug displacement and possible abscessing. Clinical trials with Laminil were conducted
without any concurrent medication, but data from the drug studies suggest that possible
interaction between the drug and bute and or banamine may occur if used concurrently.
We recommend at least 6 hours discontinuation of phenylbutazone and/or banamine
before and after infusion of Laminil.
Laminil will not take effect until the 72-hour mark on acute cases.