Pharmacologic properties of high-dose ambroxol in four patients with Gaucher disease and myoclonic epilepsy.
J Med Genet
; 57(2): 124-131, 2020 02.
Article
in En
| MEDLINE
| ID: mdl-31649052
ABSTRACT
BACKGROUND:
Ambroxol (ABX) has been suggested as an augmentative pharmacological agent for neuronopathic Gaucher disease (nGD). This study assessed the long-term safety and efficacy of combined therapy with high-dose ABX and enzyme replacement therapy (ERT) in nGD.METHODS:
ABX+ERT therapy was administered for 4.5 years in four patients with nGD. ABX was initiated at a dose of 1.5 mg/kg/day, and the dose was escalated up to 27 mg/kg/day. The target plasma level was 10 µmol/L or less. The changes in glucocerebrosidase activity, biochemical, safety and neurocognitive findings were assessed.RESULTS:
Enhanced residual GCcase activity was observed in all patients, as evidenced in both in vitro and in vivo studies. During the first 2 years of study with ABX (up to 21 mg/kg/day), mean seizure frequencies and neurocognitive function worsened. After ABX dosage was increased up to 27 mg/kg/day of ABX, its trough plasma concentration was 3.2-8.8 µmol/L. Drug-to-drug interaction, especially with antiepileptic drug significantly affected the pharmacokinetic parameters of ABX. Importantly, at 27 mg/kg/day of ABX, the seizure frequencies markedly decreased from the baseline, and the neurocognitive function was improved. In addition, Lyso-Gb1, a biomarker for the severity and progression of GD, was normalised in all patients. High-dose ABX was well-tolerated with no severe adverse events.CONCLUSIONS:
Long-term treatment with high-dose ABX+ERT was safe and might help to arrest the progression of the neurological manifestations in GD.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Epilepsies, Myoclonic
/
Enzyme Replacement Therapy
/
Ambroxol
/
Gaucher Disease
Limits:
Adolescent
/
Child
/
Female
/
Humans
/
Male
Language:
En
Journal:
J Med Genet
Year:
2020
Document type:
Article