Endogenous release of tissue factor pathway inhibitor by topical application of an ointment containing mucopolysaccharide polysulfate to nonhuman primates.
Several studies have shown that tissue factor pathway inhibitor (TFPI) is released after the intravenous and subcutaneous administration of heparin and heparin-related drugs. Mucopolysaccharide polysulfate (MPS) is a preparation of glycosaminoglycans (GAGS) derived from mammalian cartilage, which has several structural and functional properties similar to heparin. Previous reports have shown that MPS is capable of releasing TFPI after intravenous administration. Therefore, this investigation was performed to determine the ability of topically administered MPS to release TFPI in a nonhuman primate model. A group of four monkeys were administered 3% MPS ointment in a dosage of 0.5 g/kg corresponding to 15 mg MPS/kg; another four monkeys were administered placebo ointment at a dosage of 0.5 g/kg once a day for 5 days in a period of 10 days. No effect of MPS was observed on the coagulation assays activated partial thromboplastin time (APTT), thrombin time (TT) and Heptest or on the platelet count. However, both the total and free TFPI levels were significantly and progressively elevated over the 10-day period in comparison to the placebo control group (P<.05). It is proposed that the ability of the topically administered MPS to increase the free and total TFPI levels may be one of the modes of action that contributes to the anticoagulant and anti-inflammatory actions of this agent.
Hoppensteadt
D A
DA
Department of Pathology, Loyola University Chicago, 2160 S> First Avenue, Maywood, IL 60153, USA. dhoppen@lumc.edu
Fareed
J
J
Raake
P
P
Raake
W
W
D000279:Administration, Cutaneous; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D001780:Blood Coagulation Tests; D004353:Drug Evaluation, Preclinical; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D065427:Factor Xa Inhibitors; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D006025:Glycosaminoglycans / Q000008:administration & dosage / Q000494:pharmacology*; D008074:Lipoproteins / Q000032:analysis / Q000378:metabolism*; D008253:Macaca mulatta; D008297:Male; D009824:Ointments; D010976:Platelet Count
D000894:Anti-Inflammatory Agents, Non-Steroidal; D065427:Factor Xa Inhibitors; D005343:Fibrinolytic Agents; D006025:Glycosaminoglycans; D008074:Lipoproteins; D009824:Ointments; C051928:lipoprotein-associated coagulation inhibitor; C052717:mucopolysaccharide polysulfate