Methods of therapeutic monitoring of phenylacetic acid prodrugs
AssigneeHorizon Therapeutics, LLC
InventorsBruce Scharschmidt, Masoud Mokhtarani
Life of this patent
Estimating the term…
Abstract
The present disclosure provides methods for adjusting the dosage of PAA prodrugs (e.g., HPN-100, PBA) based on measurement of PAA and PAGN in plasma and calculating the PAA:PAGN ratio so as to determine whether PAA to PAGN conversion is saturated.
Claims13
A method of treating a nitrogen retention disorder in a subject comprising:
- (a) administering a first dosage of a PAA prodrug,
- (b) measuring plasma PAA and PAGN levels,
- (c) calculating a plasma PAA:PAGN ratio,
- (d) determining whether the PAA prodrug dosage needs to be adjusted based on whether the PAA:PAGN ratio falls within a target range, where a PAA:PAGN ratio below the target range indicates that the dosage potentially needs to be increased and a PAA:PAGN ratio above the target range indicates that the dosage needs to be decreased, and
- (e) administering a second dosage of the PAA prodrug based on the determination in (d).
A method of treating a nitrogen retention disorder in a subject who has previously been administered a first dosage of a PAA prodrug comprising:
- (a) measuring plasma PAA and PAGN levels,
- (b) calculating a plasma PAA:PAGN ratio,
- (c) determining whether the first PAA prodrug dosage needs to be adjusted based on whether the PAA:PAGN ratio falls within a target range, where a PAA:PAGN ratio below the target range indicates that the dosage potentially needs to be increased and a PAA:PAGN ratio above the target range indicates that the dosage needs to be decreased, and
- (d) administering a second dosage of the PAA prodrug based on the determination in (c).
(canceled)
(canceled)
A method of adjusting the dosage of a PAA prodrug comprising:
- (a) administering a first dosage of a PAA prodrug,
- (b) measuring plasma PAA and PAGN levels,
- (c) calculating a plasma PAA:PAGN ratio,
- (d) determining whether the PAA prodrug dosage needs to be adjusted based on whether the PAA:PAGN ratio falls within a target range, where a PAA:PAGN ratio below the target range indicates that the dosage potentially needs to be increased and a PAA:PAGN ratio above the target range indicates that the dosage needs to be decreased, and
- (e) administering a second dosage of the PAA prodrug based on the determination in (d).
A method of optimizing the therapeutic efficacy of a PAA prodrug in a subject who has previously been administered a first dosage of a PAA prodrug comprising:
- (a) measuring plasma PAA and PAGN levels,
- (b) calculating a plasma PAA:PAGN ratio,
- (c) determining whether the PAA prodrug dosage needs to be adjusted based on whether the PAA:PAGN ratio falls within a target range, where a PAA:PAGN ratio below the target range indicates that the dosage potentially needs to be increased and a PAA:PAGN ratio above the target range indicates that the dosage needs to be decreased, and
- (e) administering a second dosage of the PAA prodrug as necessary based on the determination in (c).
(canceled)
Dependencies are inferred from the claim text.