Unknown

Dataset Information

0

Population Pharmacokinetics/Pharmacodynamics of 3,4-Diaminopyridine Free Base in Patients With Lambert-Eaton Myasthenia.


ABSTRACT: Lambert-Eaton myasthenia (LEM) is a rare autoimmune disorder associated with debilitating muscle weakness. There are limited treatment options and 3,4-diaminopyridine (3,4-DAP) free base is an investigational orphan drug used to treat LEM-related weakness. We performed a population pharmacokinetic/pharmacodynamic (PK/PD) analysis using 3,4-DAP and metabolite concentrations collected from a phase II study in patients with LEM. The Triple Timed Up & Go (3TUG) assessment, which measures lower extremity weakness, was the primary outcome measure. A total of 1,270 PK samples (49 patients) and 1,091 3TUG data points (32 randomized patients) were included in the PK/PD analysis. A two-compartment and one-compartment model for parent and metabolite, respectively, described the PK data well. Body weight and serum creatinine partially explained the variability in clearance for the final PK model. A fractional inhibitory maximum effect (Emax ) model characterized the exposure-response relationship well. The PK/PD model was applied to identify a suggested dosing approach for 3,4-DAP free base.

SUBMITTER: Thakkar N 

PROVIDER: S-EPMC5613184 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

altmetric image

Publications

Population Pharmacokinetics/Pharmacodynamics of 3,4-Diaminopyridine Free Base in Patients With Lambert-Eaton Myasthenia.

Thakkar Nilay N   Guptill Jeffrey T JT   Aleš Kathy K   Jacobus David D   Jacobus Laura L   Peloquin Charles C   Cohen-Wolkowiez Michael M   Gonzalez Daniel D  

CPT: pharmacometrics & systems pharmacology 20170724 9


Lambert-Eaton myasthenia (LEM) is a rare autoimmune disorder associated with debilitating muscle weakness. There are limited treatment options and 3,4-diaminopyridine (3,4-DAP) free base is an investigational orphan drug used to treat LEM-related weakness. We performed a population pharmacokinetic/pharmacodynamic (PK/PD) analysis using 3,4-DAP and metabolite concentrations collected from a phase II study in patients with LEM. The Triple Timed Up & Go (3TUG) assessment, which measures lower extre  ...[more]

Similar Datasets

| S-EPMC5900968 | biostudies-literature
| S-EPMC7357813 | biostudies-literature
| S-EPMC9868566 | biostudies-literature
| S-EPMC8594444 | biostudies-literature
| S-EPMC10188401 | biostudies-literature
| S-EPMC5521354 | biostudies-other
| S-EPMC7324357 | biostudies-literature
| S-EPMC4335987 | biostudies-literature
| S-EPMC7080283 | biostudies-literature
| S-EPMC3088186 | biostudies-other