Properties and adverse effects
Pentosan is a polymer produced from xylan, which is a complex hemicellulose extract from the beechwood plant. It can be formulated
as a sodium salt or a calcium derivative. And it can be administered orally, intramuscularly, intravenously or intra-articularly.
The calcium derivative is absorbed orally and subcutaneously much more efficiently than the sodium salt, which is primarily
Adverse effects of PPS use are related to its primary function as an anticlotting or thrombolytic agent and are dose-dependent.
It's not recommended for use in postsurgical cases, for horses with autoimmune problems or prior bleeding issues or in situations
in which trauma and possible bleeding could occur.
These concerns bring the two aspects of PPS into conflict, since the typical situation in which osteoarthritis becomes a problem
requiring treatment is in performance sport horses, yet it's exactly this use that's most likely to result in possible trauma,
injury and bleeding. This was the dilemma that, at least in part, initially prevented more widespread use of PPS in athletic
Attention to dosage and frequency resulted in relatively safe use over time, however, and veterinarians and trainers in Australia
and Europe became comfortable with its use. PPS was routinely used in racehorses throughout those regions, with no documented
increase in problems associated with exercise-induced pulmonary hemorrhage or other performance-related bleeding problems.
Statistics from Biopharm Australia Pty. Ltd., the company that produces and distributes PPS in that country (where it's sold
as Cartrophen Equine Forte), indicate that only 14 adverse drug reactions occurred during a 14-year period ending in August
2007.1 Most adverse responses (13 of 14) were injection-site reactions, and company researchers concluded that the reports represent
a low incidence (less than 0.01 percent) of adverse events on an individual dose basis in horses.
In addressing possible bleeding problems, a group of researchers reported that when PPS was administered at the recommended
dose of 3 mg/kg, activated partial prothrombin time (PPT)—a standard measure of the clotting mechanism in the body—did not
return to baseline until 24 hours after injection.2 Thus, the researchers concluded that it's best to not administer PPS at doses up to 3 mg/kg within 24 hours of high-stress
activities or in situations in which physical injury could occur.
Some veterinarians administer higher PPS doses (up to 6 mg/kg) because of a perceived greater antiosteoarthritis effect. At
this dosage, the PTT returns to normal within 48 hours of administration, so the timing of PPS treatment becomes very important
in sport horses.
The anticoagulant effect of PPS is mild and is between one-sixth and one-tenth that of sodium heparin, which is the most commonly
used medical anticoagulant.3 Furthermore, PPS releases tissue plasminogen activator from the endothelium, or the lining of the blood vessels.3 It's this action that brings about the enzymatic breakdown of thrombolytic emboli or blood clots within blood vessels, and
PPS doesn't affect the systemic blood-clotting system. This recently explained distinction helps make calculated use of PPS
safer for exercising horses and potentially more worthwhile.
PPS affects arthritic joints in several ways. It has no analgesic or primary pain-relieving effects in and of itself, but
its ability to influence the overall health of the equine joint has led to its being classified as a structure-modifying osteoarthritic
drug. These compounds treat the cause of the arthritis process rather than simply alleviate the pain produced by that process.
PPS stimulates the synthesis of proteoglycans and increases the amount of these substances incorporated into the extracellular
matrix; this is the supporting structure of the cartilage that makes up the joint's weight-bearing surface. Athletic use over
time tends to cause progressive osteoarthritis or joint wear and tear, and it's the slow loss of proteoglycans from the cartilage
matrix that weakens the joint's structure and causes lameness and loss of athletic use. The drug's ability to replace these
components within the matrix is instrumental to its capacity to halt the progression of arthritis.
PPS also stimulates synovial fibroblasts (cells that make up the joint capsule) to produce increased amounts of high-molecular-weight
hyaluronic acid. These actions improve the viscosity and volume of the joint fluid that lubricates and stabilizes the joint
and helps limit further degradation of joint cartilage. Additionally, PPS inhibits and modulates inflammatory mediators including
histamine, serotonin, superoxide free radicals and proteins of the complement system, which have all been implicated in the
degradation of cartilage matrix.
Initial interest in PPS stemmed from its ability to break up fibrin, a major component of blood clots. Since cartilage has
no intrinsic blood supply, it depends on underlying bone for the vessels needed to bring necessary nutrients. The osteoarthritis
process erodes some joint surfaces and thickens other areas, which can cause a great reduction in blood flow and, thus, in
nutritional support of cartilage. The deposition of fats and fibrin into the underlying joint-related vessels of stressed
equine athletes can cause them to become clogged, which further reduces blood flow and contributes to cartilage degeneration.
PPS has specific activities that remove fibrin clots and lipids (fats) from blood vessels, and that translates into better
blood flow, reduced degeneration within the joint and eventual reduction in joint pain.