A maturation model for midazolam clearance.
Paediatr Anaesth
; 21(3): 302-8, 2011 Mar.
Article
en En
| MEDLINE
| ID: mdl-20704661
ABSTRACT
BACKGROUND:
Physiological-based pharmacokinetic models have been used to describe midazolam clearance (CL) maturation. There are no maturation descriptors of CL from neonate to adulthood based on reported estimates at different ages.METHODS:
Published CL estimates after intravenous administration from time-concentration profiles were used to construct a maturation model based on size and age. Curve fitting was performed using nonlinear mixed effects models.RESULTS:
There were 16 publications reporting an estimate of CL after intravenous administration in children, although few estimates were available from 44-80 weeks postmenstrual age (PMA). CL maturation, standardized to a 70 -kg person was described using the Hill equation. Mature CL was 523 (CV 32%, 95%CI 469, 597) ml·min(-1) ·70 kg(-1) . The maturation half-time was 73.6 (95%CI 59.4, 80.0) weeks PMA and the Hill coefficient 3 (95%CI 2.2, 4.1). Predicted CL changes with age based on this model were in close agreement with physiologically based pharmacokinetic (PBPK) models. A comparison with a published PBPK model predictions revealed a root mean squared prediction error (precision) of 4.0% (95%CI 1.1, 5.8) and bias was -0.9% (95%CI -4.3, 2.6).CONCLUSIONS:
Previously published pharmacokinetic parameters can be used to develop maturation models that address gaps in current knowledge regarding the influence of age on a drug's disposition. If a midazolam sedation target concentration of 0.1 mg·l(-1) , similar to that given to adults, is assumed, then we might anticipate steady-state infusion rates of 0.014 mg·kg(-1) ·h(-1) in neonates, 0.05 mg·kg(-1) ·h(-1) in a 1-year-old, 0.06 mg·kg(-1) ·h(-1) in a 5-year-old and 0.05 mg·kg(-1) ·h(-1) in a 12-year-old child. Age-related pharmacodynamic differences that will affect dose and the impact of active metabolites on response are not yet quantified.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Midazolam
/
Envejecimiento
/
Hipnóticos y Sedantes
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Adolescent
/
Child
/
Child, preschool
/
Female
/
Humans
/
Infant
/
Male
/
Newborn
/
Pregnancy
Idioma:
En
Revista:
Paediatr Anaesth
Asunto de la revista:
ANESTESIOLOGIA
/
PEDIATRIA
Año:
2011
Tipo del documento:
Article
País de afiliación:
Nueva Zelanda