Allometric relationships between the pharmacokinetics of propofol in rats, children and adults

Knibbe, Catherijne A. J.; Zuideveld, Klaas P.; Aarts, Leon; Kuks, Paul F. M.; Danhof, Meindert

doi:10.1111/j.1365-2125.2005.02239.x

Cited by 72 publications

(56 citation statements)

References 20 publications

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“…27,28 However, to our knowledge, there has been little discussion of the influence of these factors on serum marker estimation after TBI, though allometric estimation of the pharmacokinetics of anesthetics in the blood compartment in infants and children has been performed (y = 1.2 · body weight 1.1 ). 29 As a first attempt, we used a single-compartment pharmacokinetic model, for which the concentration of serum marker is directly proportional to the administered ''dose,'' and inversely proportional to its volume of distribution. The distribution volume of marker in this singlecompartment model is assumed to be the blood volume, which changes in relation to body weight developmentally in piglets, as it does in infants and toddlers.…”

Section: Discussionmentioning

confidence: 99%

Neuron-Specific Enolase, but Not S100B or Myelin Basic Protein, Increases in Peripheral Blood Corresponding to Lesion Volume after Cortical Impact in Piglets

Costine

Quebeda-Clerkin²,

Dodge³

et al. 2012

Journal of Neurotrauma

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A peripheral indicator of the presence and magnitude of brain injury has been a sought-after tool by clinicians. We measured neuron-specific enolase (NSE), myelin basic protein (MBP), and S100B, prior to and after scaled cortical impact in immature pigs, to determine if these purported markers increase after injury, correlate with the resulting lesion volume, and if these relationships vary with maturation. Scaled cortical impact resulted in increased lesion volume with increasing age. Concentrations of NSE, but not S100B or MBP, increased after injury in all age groups. The high variability of S100B concentrations prior to injury may have precluded detection of an increase due to injury. Total serum markers were estimated, accounting for the allometric growth of blood volume, and resulted in a positive correlation of both NSE and S100B with lesion volume. Even with allometric scaling of blood volume and a uniform mechanism of injury, NSE had only a fair to poor predictive value. In a clinical setting, where the types of injuries are varied, more investigation is required to yield a panel of serum markers that can reliably predict the extent of injury. Allometric scaling may improve estimation of serum marker release in pediatric populations.

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Section: Discussionmentioning

confidence: 99%

Neuron-Specific Enolase, but Not S100B or Myelin Basic Protein, Increases in Peripheral Blood Corresponding to Lesion Volume after Cortical Impact in Piglets

Costine

Quebeda-Clerkin²,

Dodge³

et al. 2012

Journal of Neurotrauma

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“…Neonates [17] Twenty-five cardiovascularly and respiratory stable neonates with a median of bodyweight of 2.82 (range 0.68-4.03) kg, post-natal age of 8 (1-25) days and gestational age of 37 (26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40) weeks were given an intravenous bolus dose of propofol (3 mg kg −1 ) for the elective removal of chest tubes, (semi)elective chest tube placement or endotracheal intubation.…”

Section: Subjects Of the Original Studiesmentioning

confidence: 99%

The allometric exponent for scaling clearance varies with age: a study on seven propofol datasets ranging from preterm neonates to adults

Wang

Allegaert

Peeters

et al. 2013

Brit J Clinical Pharma

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AIMFor scaling clearance between adults and children, allometric scaling with a fixed exponent of 0.75 is often applied. In this analysis, we performed a systematic study on the allometric exponent for scaling propofol clearance between two subpopulations selected from neonates, infants, toddlers, children, adolescents and adults. METHODSSeven propofol studies were included in the analysis (neonates, infants, toddlers, children, adolescents, adults1 and adults2). In a systematic manner, two out of the six study populations were selected resulting in 15 combined datasets. In addition, the data of the seven studies were regrouped into five age groups (FDA Guidance 1998), from which four combined datasets were prepared consisting of one paediatric age group and the adult group. In each of these 19 combined datasets, the allometric scaling exponent for clearance was estimated using population pharmacokinetic modelling (NONMEM 7.2). RESULTSThe allometric exponent for propofol clearance varied between 1.11 and 2.01 in cases where the neonate dataset was included. When two paediatric datasets were analyzed, the exponent varied between 0.2 and 2.01, while it varied between 0.56 and 0.81 when the adult population and a paediatric dataset except for neonates were selected. Scaling from adults to adolescents, children, infants and neonates resulted in exponents of 0.74, 0.70, 0.60 and 1.11 respectively.

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“…In an earlier study, Knibbe et al found that TRG level and relative body temperature appeared to be signiˆcant covariates for elimination clearance. 23) Studies have shown that heparin activates lipoprotein lipase and therefore results in a rapid and signiˆcant decrease in TRG immediately after heparinization; this results in an increase in circulating glycerol and free fatty acids. [24][25][26] Similar results were seen in TRG during CPB in the present study.…”

Section: Discussionmentioning

confidence: 99%

Effects of Propofol and Midazolam on Lipids, Glucose, and Plasma Osmolality during and in the Early Postoperative Period Following Coronary Artery Bypass Graft Surgery: A Randomized Trial

et al. 2007

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It is not clear how levels of serum lipids and glucose and plasma osmolality change during propofol infusion in the pre-and postoperative period of coronary artery bypass graft surgery (CABG). This prospective, randomized, controlled trial evaluated changes in these parameters during propofol or midazolam infusion during and in the early postoperative period following surgery. Twenty patients undergoing CABG were randomized preoperatively into two groups: 10 patients received propofol (induction 1.5 mg/kg, maintenance 1.5 mg kg -1 h -1 ) and 10 patients received midazolam (induction 0.5 mg/kg, maintenance 0.1 mg kg -1 h -1 ). Both groups also received fentanyl (induction 20 mg/ kg, maintenance 10 mg kg -1 ). Serum lipids, glucose, and plasma osmolality were measured preinduction, precardiopulmonary bypass, at the end of cardiopulmonary bypass, at the end of surgery, and 4 and 24 h postoperatively. In the propofol group, we observed a signiˆcant increase in triglycerides and very low-density lipoprotein levels 4 h postoperatively. In the midazolam group, we observed a signiˆcant decrease in low-density lipoprotein, cholesterol at the end of cardiopulmonary bypass, end of surgery, and 4 and 24 h postoperatively and signiˆcant increase in osmolality at the end of cardiovascular bypass. Changes in glucose levels did not diŠer signiˆcantly diŠerent between the two groups. In patients with normal serum lipids, glucose, and plasma osmolality undergoing CABG, propofol infusion for maintenance anesthesia is not associated with dangerous changes in serum lipids, glucose, and plasma osmolality compared with midazolam. A propofol infusion technique for maintenance of anesthesia for cardiac surgery where serum lipids and glucose may be of concern could be recommended as an alternative to midazolam.

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Allometric relationships between the pharmacokinetics of propofol in rats, children and adults

Cited by 72 publications

References 20 publications

Neuron-Specific Enolase, but Not S100B or Myelin Basic Protein, Increases in Peripheral Blood Corresponding to Lesion Volume after Cortical Impact in Piglets

Neuron-Specific Enolase, but Not S100B or Myelin Basic Protein, Increases in Peripheral Blood Corresponding to Lesion Volume after Cortical Impact in Piglets

The allometric exponent for scaling clearance varies with age: a study on seven propofol datasets ranging from preterm neonates to adults

Effects of Propofol and Midazolam on Lipids, Glucose, and Plasma Osmolality during and in the Early Postoperative Period Following Coronary Artery Bypass Graft Surgery: A Randomized Trial

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