Pharmacokinetics in Children: History, Considerations, and Applications

Suggs, Deanna M.

doi:10.1111/j.1745-7599.2000.tb00188.x

Cited by 4 publications

(3 citation statements)

References 7 publications

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“…7,8 Hence, when equivalent amounts of vancomycin per patient weight are administered to pediatric patients, their serum concentrations tend to be lower than those in adult patients. Additionally, in pediatric patients, over 60% of the body composition is water, [34][35][36] which dilutes vancomycin concentrations. Due to differences in the volume of distribution and high CrCl in pediatrics, relationships between trough concentrations and AUC might be different than in adults, and therefore might influence the relationship between trough levels and outcomes.…”

Section: Discussionmentioning

confidence: 99%

“…Due to differences in the volume of distribution and high CrCl in pediatrics, relationships between trough concentrations and AUC might be different than in adults, and therefore might influence the relationship between trough levels and outcomes. [34][35][36] Of note was that the clinical outcomes significantly associated with the differential trough levels at initial steady state were the risks of long-term therapy, retreatment, and frequent dose adjustments that were substantially elevated in the lowertrough group with <5 mg/L levels. Meanwhile, the study findings showed no statistically significant improvement in other clinical and microbiological outcomes (cure, death, length of hospital stay, resistant GPB isolation, and adverse renal events) with high-troughs at initial steady state compared to <5 mg/L troughs.…”

Section: Discussionmentioning

confidence: 99%

“…In consideration of vancomycin PK characteristics and body composition differences in pediatric patients, 7,8,[34][35][36] aiming for a higher-trough at initial steady state can be beneficial for disease management of pediatric infectious disease cases requiring vancomycin therapy, particularly by reducing the risk of treatment prolongation and recurrent infection as well as the need for frequent TDM-guided dose adjustment. Due to the narrow therapeutic index, TDM services are commonly provided for vancomycin-treated patients in the hospital.…”

Section: Discussionmentioning

confidence: 99%

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<p>Vancomycin Dosage and Its Association with Clinical Outcomes in Pediatric Patients with Gram-Positive Bacterial Infections</p>

Shin

Jung

Jeon

et al. 2020

RMHP

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The aim of this study was to evaluate whether vancomycin trough concentrations at initial steady state are associated with clinical and microbiological outcomes along with vancomycinrelated nephrotoxicity in pediatric patients with Gram-positive bacterial (GPB) infections. Methods: A retrospective cohort study of pediatric patients who received vancomycin for ≥72 hours during 2008-2016 was conducted. Study patients were divided into three cohorts in accordance with their first trough levels at steady state: <5 mg/L (lower-trough), 5-10 mg/ L (low-trough), and >10 mg/L (high-trough; reference) cohorts. Results: Of the 201 patients eligible for study inclusion, 60 patients in the lower-and lowtrough cohorts, respectively, were idect 3ntified via propensity score matching and analyzed against 30 high-trough patients in each comparison pair (neonates were excluded due to small sample size). Lower-trough patients were at a greater risk for prolonged therapy, retreatment, and dose adjustment than high-trough patients. Final steady-state troughs remained substantially lower in both the lower-and low-trough cohorts (p<0.001 and p=0.005, respectively), despite greater dose up-titration in the lower-trough cohort and percent change in daily dose in both the lower-and low-trough cohorts than in the high-trough cohort (p<0.001 for all). Clinical cure and death risk, along with the risks of isolation of resistant strains and renal events, were not significantly different between cohorts in both comparison pairs. Conclusion: Vancomycin troughs of <5 mg/L at initial steady state were associated with significantly compromised clinical outcomes in terms of risk of therapy prolongation, retreatment, and aggressive dose up-titration, compared to >10 mg/L troughs in pediatric patients with GPB infections.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

<p>Vancomycin Dosage and Its Association with Clinical Outcomes in Pediatric Patients with Gram-Positive Bacterial Infections</p>

Shin

Jung

Jeon

et al. 2020

RMHP

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Different pharmacokinetics of tramadol in mothers treated for labour pain and in their neonates

Grinten

Verbruggen

Berg

et al. 2005

Eur J Clin Pharmacol

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The intramuscular application of tramadol in birth-giving mothers almost freely reaches the neonate, confirming a high degree of placental permeability. The neonates already possess the complete hepatic capacity for the metabolism of tramadol into its active metabolite. However, the renal elimination of the active tramadol metabolite M1 is delayed, in line with the slow maturation process of renal function in neonates. Despite this difference in pharmacokinetics between neonates and adults, the intramuscular application of tramadol at the recommended dosage range during delivery appears to effective in the relief of labour pain.

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Population pharmacokinetic and pharmacodynamic model of propofol externally validated in children

Choi

Lee

Byon

et al. 2015

J Pharmacokinet Pharmacodyn

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There have been no pharmacokinetic parameters and blood-brain equilibration rate constant (k e0) of propofol obtained in a single population of children, by which propofol can be administered using a target effect-site concentration controlled infusion. Thirty-nine, American Society of Anesthesiologists Physical Status 1-2 children aged 2-12 years were given an intravenous bolus of propofol (3 mg kg(-1)), followed by infusion (200 µg kg(-1) min(-1)). Arterial drug concentrations and bispectral index (BIS) values were measured. Population pharmacokinetic and pharmacodynamic analysis was performed using nonlinear mixed effects modeling. External model validation was performed in a separate population of children. A two-compartment model and a sigmoid E max model directly linked by an effect compartment well described the time courses of propofol concentration and BIS. The estimates of parameters were: V 1 (L) = 1.69, V 2 (L) = 27.2 + 0.929 × (weight - 25), Cl (L min(-1)) = 0.893 × (weight/23.6)(0.966), Q (L min(-1)) = 1.3; E 0 = 76.9; E max = 35.4, Ce 50 (μg mL(-1)) = 3.47 - (0.095 × age) - (1.63 × mean infusion rate of remifentanil in µg kg(-1) min(-1)); γ = 2.1; and k e0 (min(-1)) = 0.371. Pooled biases (95 % CI) of the target effect-site concentration controlled infusion system of propofol was -20.2 % (-23.3 to -18.1 %) and pooled inaccuracy was 30.4 % (28.6-32.7 %). Pooled biases of BIS prediction was -6.8 % (-9.1 to -4.1 %) and pooled inaccuracies was 19.1 % (17.5-20.9 %).The altered weight-based dose requirements of propofol are well described pharmacokinetically, and pharmacodynamically. Predictive performances of the TCI system in this study were clinically acceptable.

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Pharmacokinetics in Children: History, Considerations, and Applications

Cited by 4 publications

References 7 publications

<p>Vancomycin Dosage and Its Association with Clinical Outcomes in Pediatric Patients with Gram-Positive Bacterial Infections</p>

<p>Vancomycin Dosage and Its Association with Clinical Outcomes in Pediatric Patients with Gram-Positive Bacterial Infections</p>

Different pharmacokinetics of tramadol in mothers treated for labour pain and in their neonates

Population pharmacokinetic and pharmacodynamic model of propofol externally validated in children

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