UNASSIGNED: The objectives of this work were first to describe the pharmacokinetic (PK) of @entity15726 and its active metabolite in a paediatric @entity1 population after repeated oral administration of @entity15726 using a population PK approach, and secondly to assess whether the blood/plasma ratio and the pharmacokinetic/pharmacodynamic (PK/ @entity1726 ) relationship are preserved in the paediatric population in comparison to adult. PK data for 70 @entity1 were obtained after blood sampling using dried blood spot and one plasma sample in order to assess the relationship between blood and plasma concentration. In order to describe @entity15726 and its metabolite blood concentrations in @entity1 , a joint population PK model was developed taking into account weight _ age effects on PK parameters. Plasma PK exposure parameters were calculated in @entity1 using plasma PK profiles. In order to assess the PK/ @entity1726 relationship in @entity1 , an adult PK/ @entity1726 model was used. The relationship between blood and plasma concentrations was described using linear mixed effect models. Two and one-compartment models best described parent and metabolite dispositions. Weight effects were fixed to the allometric values of    on clearance (CL) and 1 on volume. A maturation function was added on metabolite formation clearance (CL PM ) reflecting enzyme maturation. Plasma exposure comparison indicated that higher dose/kg were necessary to achieve a similar exposure between younger and older @entity1 . No differences between age classes were observed in terms of range of exposure at the maintenance dose. The PK/ @entity1726 relationship in adult @entity1 is conserved in @entity1 .

Model-based approaches for @entity15726 development in paediatric population, part II: PK and PK/ XXXX assessment.

@entity1 :: ('9606', 'Species') :: ['children', 'patients', 'patient'] @entity1726 :: ('OMIM:168600', 'Disease') :: ['PD'] @entity15726 :: ('MESH:C088408', 'Chemical') :: ['ivabradine']
@entity1726 :: (OMIM:168600,Disease) :: ['PD']
