Disentangling PK-PD in neonates

Anderson, Brian J.

doi:10.1136/fn.89.1.f3-a

Cited by 11 publications

(6 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The cause of this finding is uncertain; relative organ Size has considerable impact on the estimation and interpretation of PK parameters in neonates 6 15 and is often unaccounted for in neonatal pharmacokinetic studies. 6 Size was the primary covariate used in our analysis of the effects of age and weight. This deliberate choice was based on known biological principles.…”

Section: Discussionmentioning

confidence: 99%

Morphine pharmacokinetics and pharmacodynamics in preterm and term neonates: secondary results from the NEOPAIN trial

Anand

Anderson

Holford

et al. 2008

British Journal of Anaesthesia

164

133

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

Morphine pharmacokinetics and pharmacodynamics in preterm and term neonates: secondary results from the NEOPAIN trial

Anand

Anderson

Holford

et al. 2008

British Journal of Anaesthesia

164

133

View full text Add to dashboard Cite

show abstract

“…Size has considerable impact on the variability of PK parameters in children and is often unaccounted for in neonatal PK studies [11, 12, 23]. Size was the primary covariate used in our analysis of the effects of age and weight.…”

Section: Discussionmentioning

confidence: 99%

Limited predictability of amikacin clearance in extreme premature neonates at birth

Allegaert¹,

Anderson²,

Cossey³

et al. 2005

Brit J Clinical Pharma

View full text Add to dashboard Cite

AimIdentify and quantify factors describing variability of amikacin clearance in preterm neonates at birth. MethodsPopulation pharmacokinetics of amikacin were estimated in a cohor t of 205 extreme preterm neonates [post conception age (PCA) 27.8, SD 1.8, range 24-30 weeks; weight 1.07, SD 0.34, range 0.45-1.98 kg, postnatal age < 72 h]. Covariate analysis included weight, PCA, Apgar score, prophylactic administration of a nonsteroidal antiinflammatory drug (NSAID) to the neonate, maternal indomethacin and betamethasone administration, and chorioamnionitis. ConclusionsSize and post-conception age are the major contributors to clearance variability in extreme premature neonates ( < 31 weeks PCA). The large (35% of total) unexplained variability in clearance reinforces the need for target concentration intervention to reduce variability in exposure to a safe and effective range.

show abstract

“…While PCA is physiologically appropriate to explain the time course of changes in clearance, PMA is used pragmatically because the first day of a menstrual period is more easily documented than the day of conception. After standardization for growth using allometric theory, the maturation of drug clearance in the first few years of life is often describable using PMA …”

Section: Introductionmentioning

confidence: 99%

Negligible impact of birth on renal function and drug metabolism

Anderson

Holford

2018

Pediatric Anesthesia

View full text Add to dashboard Cite

Summary Background Transition from the intrauterine to the extrauterine environment in neonates is associated with major changes in blood flow and oxygenation with consequent increases in metabolic functions. The additional impact of birth on renal function and drug metabolism above that predicted by postmenstrual age and allometry is uncertain. Increased clearance at birth could reduce analgesic effect attributable to a lowering of plasma concentration. These elimination processes can be described using the clearance concept. Methods Data from four publications that investigated the time course of glomerular filtration rate and clearance of paracetamol, morphine and tramadol were reanalyzed. The effect of birth, based on postnatal age, was used in conjunction with a theory‐based allometric size scaling and maturation based on postmenstrual age. Results Postnatal age had a short‐term effect on the time course of clearance distinguishable from the well‐known slower maturation based on postmenstrual age. While elimination might be relatively reduced by 15%‐45% at birth, there is a rapid increase in elimination for 1‐3 weeks after birth to be 15% greater than that predicted by postmenstrual age alone. Conclusion Birth is associated with a small increase in clearance in addition to that described by postmenstrual age for common analgesic drugs cleared by glucuronide conjugation (morphine, paracetamol) or by the P450 cytochrome oxidase (tramadol) and renal systems. While the increase is of biological interest, it would not be expected to have any clinically relevant impact on renal function or drug dosing. The processes of maturation described by these models are potentially applicable to any drug elimination process.

show abstract

Disentangling PK-PD in neonates

Cited by 11 publications

References 11 publications

Morphine pharmacokinetics and pharmacodynamics in preterm and term neonates: secondary results from the NEOPAIN trial

Morphine pharmacokinetics and pharmacodynamics in preterm and term neonates: secondary results from the NEOPAIN trial

Limited predictability of amikacin clearance in extreme premature neonates at birth

Negligible impact of birth on renal function and drug metabolism

Contact Info

Product

Resources

About