Administration of the REG1 anticoagulation system
An improved method of administration of an aptamer and antidote system to regulate blood coagulation in a host is provided based on weight adjusted or body mass index-adjusted dosing of the components of the system to provide a desired pharmacodynamic response. In addition, a method of reversing activity of the aptamer to a desired extent is provided where an antidote dose is based solely on its relationship to the aptamer dose.
1 . A method of administration of an aptamer comprising:
a. measuring the body mass index (BMI) of a host;
b. identifying a desired pharmacodynamic response; and
c. administering to the host a dose of an aptamer to achieve a desired pharmacodynamic response based on a comparison of the dose per BMI to pharmacodynamic response.
2 . The method of claim 1 further comprising administering a dose of an antidote to the aptamer to the host where the dose of antidote is based on the known dose of aptamer previously administered, and the antidote:aptamer ratio is based on a desired reduction in aptamer activity.
3 . The method of claim 1 wherein the desired pharmacodynamic response is a maximal level of anti-coagulation.
4 . The method of claim 3 wherein the aptamer is administered at a dose of 4 mg/BMI or greater.
5 . The method of claim 1 wherein the desired pharmacodynamic response is a level of anticoagulation of about 75% maximal.
6 . The method of claim 5 wherein the aptamer is administered at a dose of about between 3.0-4.0 mg/BMI.
7 . The method of claim 1 wherein the desired pharmacodynamic response is a level of anticoagulation of about 50% maximal.
8 . The method of claim 7 wherein the aptamer is administered at a dose of about between 2.0-3.0 mg/BMI.
9 . The method of claim 1 wherein the dose of anticoagulant is between 0.1 and 10 mg/BMI.
10 . The method of claim 1 wherein the dose of anticoagulant is about 5 mg/BMI.
11 . A method of administration of an aptamer comprising:
a. measuring the weight in kg of a host;
b. identifying a desired pharmacodynamic response;
c. administering to the host a dose of an aptamer to achieve a desired pharmacodynamic response based on a comparison of the dose per kg to pharmacodynamic response; and,
d. administering a dose of an antidote to the aptamer to the host where the dose of antidote is provided based only on a ratio with aptamer
12 . The method of claim 11 further comprising administering a dose of an antidote to the aptamer to the host where the dose of antidote is based on the known dose of aptamer previously administered, and the antidote:aptamer ratio is based on a desired reduction in aptamer activity.
13 . The method of claim 11 wherein the desired pharmacodynamic response is maximal level of anti-coagulation.
14 . The method of claim 13 wherein the dose of anticoagulant is about 1.4 mg/kg or greater.
15 . The method of claim 11 wherein the desired pharmacodynamic response is a level of anticoagulation of about 75% maximal.
16 . The method of claim 15 wherein the dose of anticoagulant is about between 1.0 mg/kg.
17 . The method of claim 11 wherein the desired pharmacodynamic response is a level of anticoagulation of about 50% maximal.
18 . The method of claim 17 wherein the dose of anticoagulant is about 0.6-0.8 mg/kg.
19 . The method of claim 11 wherein the dose of anticoagulant is between 0.1 and 2 mg/kg.
20 . The method of claim 11 wherein the dose of anticoagulant is between 5 and 10 mg/kg.
21 . The method of claim 1 or 11 wherein the antidote is an oligonucleotide antidote.
22 . The method of claim 1 or 11 wherein the aptamer comprises SEQ ID NO 1.
23 . The method of claim 1 or 11 wherein the pharmacodynamic response is measured in a coagulation assay.
24 . The method of claim 1 or 11 wherein the aptamer is administered in an IV bolus delivery.
25 . The method of claim 1 or 11 wherein the aptamer is administered by subcutaneous injection.
26 . The method of claim 2 or 12 wherein aptamer and antidote are administered at a ratio of 1:1.
27 . The method of claim 2 or 12 wherein aptamer and antidote are administered at a ratio of at least 2:1.
28 . The method of claim 2 or 12 wherein aptamer and antidote are administered at a ratio of 0.5:1 or less.
29 . The method of claim 2 or 12 wherein aptamer activity is reversed by less than 90%.
30 . The method of claim 2 or 12 wherein aptamer activity is reversed by about 50%.