Population Pharmacokinetic Model of N-acetylmannosamine (ManNAc) and N-acetylneuraminic acid (Neu5Ac) in Subjects with GNE Myopathy.
Journal
Drugs in R&D
ISSN: 1179-6901
Titre abrégé: Drugs R D
Pays: New Zealand
ID NLM: 100883647
Informations de publication
Date de publication:
Jun 2021
Jun 2021
Historique:
accepted:
10
03
2021
pubmed:
25
4
2021
medline:
26
10
2021
entrez:
24
4
2021
Statut:
ppublish
Résumé
GNE myopathy is a rare genetic muscle disease resulting from deficiency in an enzyme critical for the biosynthesis of N-acetylneuraminic acid (Neu5Ac, sialic acid). The uncharged Neu5Ac precursor, N-acetylmannosamine (ManNAc), is under development as an orphan drug for treating GNE myopathy. A semi-mechanistic population pharmacokinetic model was developed to simultaneously characterize plasma ManNAc and its metabolite Neu5Ac following oral administration of ManNAc to subjects with GNE myopathy. Plasma ManNAc and Neu5Ac pharmacokinetic data were obtained from two clinical studies (ClinicalTrials.gov identifiers NCT01634750, NCT02346461) and were simultaneously modeled using NONMEM. ManNAc and Neu5Ac plasma concentrations were obtained from 34 subjects with GNE myopathy (16 male, 18 female, median age 39.5 years). The model parameter estimates included oral absorption rate (k This population pharmacokinetic model can be used to evaluate ManNAc dosing regimens and to calculate Neu5Ac production and exposure following oral administration of ManNAc in subjects with GNE myopathy.
Sections du résumé
BACKGROUND
BACKGROUND
GNE myopathy is a rare genetic muscle disease resulting from deficiency in an enzyme critical for the biosynthesis of N-acetylneuraminic acid (Neu5Ac, sialic acid). The uncharged Neu5Ac precursor, N-acetylmannosamine (ManNAc), is under development as an orphan drug for treating GNE myopathy.
METHODS
METHODS
A semi-mechanistic population pharmacokinetic model was developed to simultaneously characterize plasma ManNAc and its metabolite Neu5Ac following oral administration of ManNAc to subjects with GNE myopathy. Plasma ManNAc and Neu5Ac pharmacokinetic data were obtained from two clinical studies (ClinicalTrials.gov identifiers NCT01634750, NCT02346461) and were simultaneously modeled using NONMEM.
RESULTS
RESULTS
ManNAc and Neu5Ac plasma concentrations were obtained from 34 subjects with GNE myopathy (16 male, 18 female, median age 39.5 years). The model parameter estimates included oral absorption rate (k
CONCLUSIONS
CONCLUSIONS
This population pharmacokinetic model can be used to evaluate ManNAc dosing regimens and to calculate Neu5Ac production and exposure following oral administration of ManNAc in subjects with GNE myopathy.
Identifiants
pubmed: 33893973
doi: 10.1007/s40268-021-00343-6
pii: 10.1007/s40268-021-00343-6
pmc: PMC8206310
doi:
Substances chimiques
Hexosamines
0
N-Acetylneuraminic Acid
GZP2782OP0
N-acetylmannosamine
X80PR7P73R
Banques de données
ClinicalTrials.gov
['NCT02346461', 'NCT01634750']
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
189-202Références
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