Population pharmacokinetic analysis of ropivacaine and its metabolite 2',6'-pipecoloxylidide from pooled data in neonates, infants, and children.
Br J Anaesth
; 107(3): 409-24, 2011 Sep.
Article
en En
| MEDLINE
| ID: mdl-21693469
ABSTRACT
BACKGROUND:
The aim was to characterize ropivacaine and 2',6'-pipecoloxylidide (PPX) pharmacokinetics and factors affecting them in paediatric anaesthesia.METHODS:
Population pharmacokinetics of ropivacaine and its active metabolite PPX were estimated after single and continuous ropivacaine blocks in 192 patients aged 0-12 yr from six pooled published studies. Unbound and total ropivacaine and PPX plasma concentration and PPX urinary excretion data were used for non-linear mixed-effects modelling by NONMEM. Covariates included age, body weight, gender, ethnic origin, ASA, site and method of administration, and total dose.RESULTS:
One-compartment first-order pharmacokinetic models incorporating linear binding of ropivacaine and PPX to α(1)-acid glycoprotein were used. After accounting for the effect of body weight, clearance of unbound ropivacaine and PPX reached 41% and 89% of their mature values, respectively, at the age of 6 months. Ropivacaine half-life decreased with age from 13 h in the newborn to 3 h beyond 1 yr. PPX half-life differed from 19 h in the newborn to 8-11 h between 1 and 12 months to 17 h after 1 yr. Simulations indicate that for a single caudal block, the recommended dose could be increased by a factor of 2.9 (0-1 month group) and 6.3 (1-12 yr group) before the unbound plasma concentrations would cross the threshold for systemic toxicity. Corresponding factors for continuous epidural infusion are 1.8 and 4.9.CONCLUSIONS:
Ropivacaine and PPX unbound clearance depends on body weight and age. The results support approved dose recommendations of ropivacaine for the paediatric population.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Bupivacaína
/
Amidas
/
Anestésicos Locales
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Br J Anaesth
Año:
2011
Tipo del documento:
Article