US 11,808,759 B2
Treatment methods having reduced drug-related toxicity and methods of identifying the likelihood of patient harm from prescribed medications
Jacques Turgeon, Orlando, FL (US); Lauren E. Steffen, Levittown, PA (US); Gabriel Badea, Prevost (CA); and Veronique Michaud, Orlando, FL (US)
Assigned to TABULA RASA HEALTHCARE, INC., Moorestown, NJ (US)
Filed by TABULA RASA HEALTHCARE, INC., Moorestown, NJ (US)
Filed on Jan. 7, 2021, as Appl. No. 17/143,936.
Application 17/143,936 is a continuation of application No. 16/302,824, granted, now 10,890,577, previously published as PCT/US2017/033539, filed on May 19, 2017.
Claims priority of provisional application 62/338,704, filed on May 19, 2016.
Prior Publication US 2021/0140944 A1, May 13, 2021
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 31/445 (2006.01); G01N 33/50 (2006.01); A61P 9/06 (2006.01); A61K 49/00 (2006.01); G01N 33/68 (2006.01); A61B 5/361 (2021.01); A61B 5/363 (2021.01); A61K 45/06 (2006.01)
CPC G01N 33/5014 (2013.01) [A61B 5/361 (2021.01); A61B 5/363 (2021.01); A61K 31/445 (2013.01); A61K 49/0004 (2013.01); A61P 9/06 (2018.01); G01N 33/6893 (2013.01); A61K 45/06 (2013.01); G01N 2800/326 (2013.01); G01N 2800/50 (2013.01)] 7 Claims
 
1. A method for determining whether a medication is associated with an increased risk of drug-induced long QT syndrome or Torsades de Pointes in combination with at least one other drug by determining a drug-specific index for the medication, the method comprising the steps of:
(i) calculating a first index variable by determining;
an IC50 value for block of one or more of IKr and IKs,
a Cmax of the medication at a test dose,
a daily dose amount of the medication,
a protein binding value for the medication at a target protein,
a drug-drug interaction coefficient (DDIC) for the medication, and
calculating a value for the first index variable based on the following equation:

OG Complex Work Unit Math
(ii) calculating a second index variable by determining:
an IC50 value for block of CaV1.2 current,
the IC50 value for block of one or more of IKr and IKs, and
calculating a value for the second index variable based on the following equation:

OG Complex Work Unit Math
(iii) calculating a third index variable by determining:
an IC50 value for block of NaV1.5 current,
the IC50 value for block of one or more of IKr and IKs, and
calculating a value for the third index variable based on the following equation:

OG Complex Work Unit Math
(iv) calculating a value for a fourth index variable based on whether the medication is an inhibitor of hERG trafficking; and
(v) combining the values for the first, second, third, and fourth index variables to provide the drug-specific index, wherein a drug-specific index of less than a predetermined threshold value is indicative of an increased risk of drug-induced long QT syndrome or Torsades de Pointes for the medication in combination with the at least one other drug.