Effect of hepatic and renal impairment on the pharmacokinetics of olanzapine and samidorphan given in combination as a bilayer tablet.
Drug Des Devel Ther
; 13: 2941-2955, 2019.
Article
in En
| MEDLINE
| ID: mdl-31686778
ABSTRACT
BACKGROUND:
A combination of olanzapine and samidorphan (OLZ/SAM) is in development to provide the established antipsychotic efficacy of olanzapine while mitigating olanzapine-induced weight gain.METHODS:
Two multicenter, open-label, parallel-cohort studies were performed to evaluate the effect of moderate hepatic impairment (Child-Pugh score 7-9 [class B]; study 1) and severe renal impairment (estimated glomerular filtration rate 15-29 mL/min/1.73 m2; study 2) on the pharmacokinetics, safety, and tolerability of a single dose of OLZ/SAM 5/10 mg.RESULTS:
There was a 1.67-fold increase in area under the plasma concentration-time curve from time 0 to infinity (AUC0-∞) and a 2.17-fold increase in maximum plasma concentration (Cmax) of olanzapine, and a 1.52-fold increase in AUC0-∞ and a 1.63-fold increase in Cmax of samidorphan, in subjects with moderate hepatic impairment compared with healthy control subjects. Compared with healthy control subjects, subjects with severe renal impairment had a 33% and 56% reduction in clearance, a 1.51- and 2.31-fold increase in AUC0-∞, and a 1.32- and 1.37-fold increase in Cmax of olanzapine and samidorphan, respectively.CONCLUSION:
OLZ/SAM 5/10 mg was generally well tolerated under the conditions of the studies, with a safety profile consistent with that observed in other clinical studies of OLZ/SAM.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Antipsychotic Agents
/
Renal Insufficiency
/
Olanzapine
/
Liver Diseases
/
Naltrexone
Type of study:
Clinical_trials
/
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Risk_factors_studies
Limits:
Adolescent
/
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Drug Des Devel Ther
Journal subject:
FARMACOLOGIA
/
TERAPIA POR MEDICAMENTOS
Year:
2019
Document type:
Article
Affiliation country:
Estados Unidos