Thiopentone elimination in newborn infants: exploring Michaelis-Menten kinetics.
Larsson, P ; Anderson, B J ; Norman, Elisabeth LU ; Westrin, Per LU and Fellman, Vineta LU
(2011)
In Acta Anaesthesiologica Scandinavica
55.
p.444-451
- Abstract
- Background: Thiopentone elimination has been described using Michaelis-Menten pharmacokinetics in adults after prolonged infusion or overdose, but there are few reports of elimination in neonates. Methods: Time-concentration profiles for neonates (n=37) given single-dose thiopentone were examined using both first-order (constant clearance) and mixed-order (Michaelis-Menten) elimination processes using nonlinear mixed effects models. These profiles included a 33-week post-menstrual age (PMA) neonate given an overdose. A two-compartment mamillary model was used to fit data. Parameter estimates were standardized to a 70 kg person using allometric models. Results: There were 197 observations available for analysis from neonates with a mean... (More)
- Background: Thiopentone elimination has been described using Michaelis-Menten pharmacokinetics in adults after prolonged infusion or overdose, but there are few reports of elimination in neonates. Methods: Time-concentration profiles for neonates (n=37) given single-dose thiopentone were examined using both first-order (constant clearance) and mixed-order (Michaelis-Menten) elimination processes using nonlinear mixed effects models. These profiles included a 33-week post-menstrual age (PMA) neonate given an overdose. A two-compartment mamillary model was used to fit data. Parameter estimates were standardized to a 70 kg person using allometric models. Results: There were 197 observations available for analysis from neonates with a mean post-menstrual age of 35 (SD 4.5) weeks and a mean weight of 2.5 (SD 0.9) kg. They were given a mean thiopentone dose of 3 (SD 0.4) mg/kg as a rapid bolus. Clearance at 26 weeks PMA was 0.015 l/min/70 kg and increased to 0.119 l/min/70 kg by 42 weeks PMA. The maximum rate of elimination (V(max) ) at 26 weeks PMA was 0.22 mg/min/70 kg and increased to 4.13 mg/min/70 kg by 42 weeks PMA. These parameter estimates are approximately 40% adult values at term gestation. The Michaelis constant (K(m) ) was 28.3 [between subject variability (BSV) 46.4%, 95% confidence interval (CI) 4.49-99.2] mg/l; intercompartment clearance was 0.44 (BSV 97.5%, 95% CI 0.27-0.63) l/min/70 kg; central volume of distribution was 46.4 (BSV 29.2%, 95% CI 41.7-59.8) l/70 kg; peripheral volume of distribution was 95.7 (BSV 70.3%, 95% CI 61.3-128) l/70 kg. Conclusions: Both first-order and mixed-order processes satisfactorily described elimination. First-order elimination adequately described the time-concentration profile in the premature neonate given an overdose. Clearance is immature in the pre-term neonate although there is rapid maturation around 40 weeks PMA, irrespective of post-natal age. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1831601
- author
- Larsson, P
; Anderson, B J
; Norman, Elisabeth
LU
; Westrin, Per
LU
and Fellman, Vineta
LU
- organization
- publishing date
- 2011
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Acta Anaesthesiologica Scandinavica
- volume
- 55
- pages
- 444 - 451
- publisher
- Wiley-Blackwell
- external identifiers
-
- wos:000288249200011
- pmid:21342147
- scopus:79952592470
- pmid:21342147
- ISSN
- 0001-5172
- DOI
- 10.1111/j.1399-6576.2010.02380.x
- language
- English
- LU publication?
- yes
- id
- 8f0e0b8d-9b0f-42c3-8b82-e8fa4066f790 (old id 1831601)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/21342147?dopt=Abstract
- date added to LUP
- 2016-04-04 08:05:21
- date last changed
- 2022-01-29 02:59:54
@article{8f0e0b8d-9b0f-42c3-8b82-e8fa4066f790,
abstract = {{Background: Thiopentone elimination has been described using Michaelis-Menten pharmacokinetics in adults after prolonged infusion or overdose, but there are few reports of elimination in neonates. Methods: Time-concentration profiles for neonates (n=37) given single-dose thiopentone were examined using both first-order (constant clearance) and mixed-order (Michaelis-Menten) elimination processes using nonlinear mixed effects models. These profiles included a 33-week post-menstrual age (PMA) neonate given an overdose. A two-compartment mamillary model was used to fit data. Parameter estimates were standardized to a 70 kg person using allometric models. Results: There were 197 observations available for analysis from neonates with a mean post-menstrual age of 35 (SD 4.5) weeks and a mean weight of 2.5 (SD 0.9) kg. They were given a mean thiopentone dose of 3 (SD 0.4) mg/kg as a rapid bolus. Clearance at 26 weeks PMA was 0.015 l/min/70 kg and increased to 0.119 l/min/70 kg by 42 weeks PMA. The maximum rate of elimination (V(max) ) at 26 weeks PMA was 0.22 mg/min/70 kg and increased to 4.13 mg/min/70 kg by 42 weeks PMA. These parameter estimates are approximately 40% adult values at term gestation. The Michaelis constant (K(m) ) was 28.3 [between subject variability (BSV) 46.4%, 95% confidence interval (CI) 4.49-99.2] mg/l; intercompartment clearance was 0.44 (BSV 97.5%, 95% CI 0.27-0.63) l/min/70 kg; central volume of distribution was 46.4 (BSV 29.2%, 95% CI 41.7-59.8) l/70 kg; peripheral volume of distribution was 95.7 (BSV 70.3%, 95% CI 61.3-128) l/70 kg. Conclusions: Both first-order and mixed-order processes satisfactorily described elimination. First-order elimination adequately described the time-concentration profile in the premature neonate given an overdose. Clearance is immature in the pre-term neonate although there is rapid maturation around 40 weeks PMA, irrespective of post-natal age.}},
author = {{Larsson, P and Anderson, B J and Norman, Elisabeth and Westrin, Per and Fellman, Vineta}},
issn = {{0001-5172}},
language = {{eng}},
pages = {{444--451}},
publisher = {{Wiley-Blackwell}},
series = {{Acta Anaesthesiologica Scandinavica}},
title = {{Thiopentone elimination in newborn infants: exploring Michaelis-Menten kinetics.}},
url = {{http://dx.doi.org/10.1111/j.1399-6576.2010.02380.x}},
doi = {{10.1111/j.1399-6576.2010.02380.x}},
volume = {{55}},
year = {{2011}},
}