Chemical formula: C₂₈₄H₄₃₂N₈₄O₇₉S₇ Molecular mass: 6,510.051 g/mol PubChem compound: 22833874
Aprotinin is a broad spectrum protease inhibitor which has antifibrinolytic properties. By forming reversible stoichiometric enzyme-inhibitor complexes, aprotinin acts as an inhibitor of human trypsin, plasmin, plasma kallikrein and tissue kallikrein, thus inhibiting fibrinolysis.
It also inhibits the contact phase activation of coagulation which both initiates coagulation and promotes fibrinolysis.
After intravenous injection, rapid distribution of aprotinin occurs into the total extracellular space, leading to an initial decrease in plasma Aprotinin concentration with a half-life of 0.3-0.7 h. At later time points, (i.e. beyond 5 hours post-dose) there is a terminal elimination phase with a half-life of about 5-10 hours.
The placenta is probably not absolutely impermeable to aprotinin, but permeation appears to take a very slow course.
The aprotinin molecule is metabolised to shorter peptides or amino acids by lysosomal activity in the kidney. In man, urinary excretion of active Aprotinin accounts for less than 5% of the dose. After receiving injections of 131Iaprotinin healthy volunteers excreted within 48 hours 25-40% of the labelled substance as metabolites in the urine. These metabolites lacked enzyme inhibitory activity.
No pharmacokinetic studies are available in patients with terminal renal insufficiency. Studies in patients with renal impairment revealed no clinically significant pharmacokinetic alterations or obvious side effects. A special dose adjustment is not warranted.
In rats, guinea-pigs, rabbits and dogs, high doses (>150,000 KIU/kg) injected quickly caused a blood pressure reduction of varying magnitude, which rapidly subsided.
In rat intravenous studies, daily doses of up to 80,000 KIU/kg produced no maternal toxicity, embryotoxicity, or foetotoxicity. Daily doses of up to 100,000 KIU/kg did not interfere with the growth and development of the young and doses of 200,000 KIU/kg/day were not teratogenic. In rabbits, daily intravenous doses of 100,000 KIU/kg produced no evidence of maternal toxicity, embryotoxicity, foetotoxicity or teratogenicity.
Aprotinin gave a negative mutagenic response in the salmonella/microsome and B. subtilis DNA damage system.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
