Anticoagulant drug-antidote combination safe for human use
Susumu Nishinaga/Science Photo Library
Coagulation could be turned on and off |
A novel approach to anticoagulation, using an RNA aptamer-antidote combination, is safe for use in humans, say US researchers.
They argue that the occurrence of bleeding as a trade-off for effective
anticoagulation is unacceptable and that there is a need for anticoagulants
with more favourable safety profiles. They point out that unfractionated-heparin,
currently the only antidote-reversible anticoagulant, has limitations
because of its complex pharmacokinetics and the fact that its antidote,
protamine sulphate, shares similar complexity and has serious cardiovascular
side effects.
The researchers tested a drug-antidote pair composed of a specific aptamer-based
inhibitor of coagulation factor IXa and its complementary oligonucleotide
antidote in 85 healthy volunteers. As expected, activated clotting time
and activated plasma thromboplastin time values were increased in subjects
treated with the agent. And antidote administration reversed the pharmacological
activity of the drug in less than five minutes.
“This novel construct represents, in essence, an anticoagulation
system that provides a rapid and effective means to either attenuate
or fully
inhibit specific coagulation proteases, while maintaining haemostatic
control through tailored administration of an inherently safe neutralising
antidote. In effect this anticoagulation system has the potential to
offer a molecular ‘on-off’ switch to pharmacologic anticoagulation.”
The data were presented at the annual
scientific sessions of the American Heart Association in Chicago this week and are published
online in Circulation.
The researchers are now testing the agent in patients with stable heart
disease. |
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Pharmaceutical Journal
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