scholarly journals P117 Dose evaluation of intravenous metamizole (dipyrone) in infants and children: a prospective population pharmacokinetic study

2019 ◽  
Vol 104 (6) ◽  
pp. e66.1-e66
Author(s):  
V Ziesenitz ◽  
F Rodieux ◽  
A Atkinson ◽  
C Borter ◽  
J Bielicki ◽  
...  
Keyword(s):  
Active Metabolite ◽  
Optimal Dose ◽  
Infants And Children ◽  
Population Pharmacokinetic ◽  
Older Children ◽  
Post Dose ◽  
Large Variability ◽  
Age Cohorts ◽  
Population Pharmacokinetic Study ◽  
In Infants And Children

BackgroundThe prodrug metamizole is frequently dosed intravenously (IV) for postoperative pain in children of all ages, despite its off-label use in infants < 1 year. We aimed to investigate the pharmacokinetics (PK) of the main metabolite of metamizole, 4-aminoantipyrine (MAA), in children aged 3–72 months following IV dosing.Methods10 mg/kg metamizole was administered IV for postoperative analgesia. PK samples were drawn at 5 predefined time points. PK of the main active metabolite MAA and three other metabolites was characterized by both non-compartmental (NCA) and population PK analysis (PPK). AUC0-inf of MAA was calculated by NCA for two age cohorts (3–23 months, 2–6 years) and compared to the 80–125% range of adult dose-adjusted reference exposure (AUCref). PPK investigated age and weight dependency of the kinetics, and dosing strategies to achieve equivalent adult exposure in children.ResultsA total of 25 children aged 5 months - 5.8 years (7.8–24.8 kg) with at least one plasma concentration sample were included in PPK, 19 children who had 5 predefined samples up to 10 h post-dose were included in NCA. AUC0-inf of MAA in children of 2–6 years was 29.8 (95%CI 23.3–38.1) mg/L*h, significantly lower than AUCref(80%-125% range: 39.2–61.2 mg/L*h). AUC0-inf of MAA in infants of 3–23 months was 42.5 (95%CI 15.7–115.4) mg/L*h, overlapping with AUCref. The large variability observed in infants could be partially explained by covariates body weight and age.ConclusionsKinetics of the main active metabolite MAA depends on age in infants and children. MAA exposure after a single IV dose of 10 mg/kg metamizole in infants < 1 year of age was higher compared to an equal dose in adults and older children. This suggests that the optimal dose for this age group to achieve equivalent exposure compared to adults is lower than currently recommended.Disclosure(s)Nothing to disclose.

scholarly journals Dose evaluation of intravenous metamizole (dipyrone) in infants and children: a prospective population pharmacokinetic study

2019 ◽  
Vol 75 (11) ◽  
pp. 1491-1502 ◽  
Author(s):  
Victoria C. Ziesenitz ◽  
Frédérique Rodieux ◽  
Andrew Atkinson ◽  
Carole Borter ◽  
Julia A. Bielicki ◽  
...  
Keyword(s):  
Pharmacokinetic Study ◽  
Infants And Children ◽  
Population Pharmacokinetic ◽  
Dose Evaluation ◽  
Population Pharmacokinetic Study ◽  
In Infants And Children

scholarly journals Endoscopic retrograde cholangiopancreatography in infants and children

2021 ◽  
Vol 09 (03) ◽  
pp. E292-E296
Author(s):  
Tone Lise Åvitsland ◽  
Lars Aabakken
Keyword(s):  
Endoscopic Retrograde Cholangiopancreatography ◽  
Medical Records ◽  
Pediatric Patients ◽  
Biliary Stricture ◽  
Infants And Children ◽  
University Hospital ◽  
Older Children ◽  
Endoscopic Retrograde ◽  
Procedure Codes ◽  
In Infants And Children

Abstract Background and study aims Previous reports have suggested that endoscopic retrograde cholangiopancreatography (ERCP) in pediatric patients are safe. However, the total number of cases presented in the literature remains small. We present results regarding safety and outcomes in pediatric patients undergoing ERCP at Oslo University Hospital. Patients and methods Patients < 18 years who underwent ERCP between April 1999 and November 2017 were identified using procedure codes. Medical records were examined for age, gender, diagnosis, indications, type of sedation, findings, interventions, and complications. Results A total of 244 procedures were performed in 158 patients. Fifty-six of these were in 53 infants (age ≤ 1 year). Mean age was 8.8 years. The youngest patient was 8 days old. Mean weight was 5.0 kg in infants, the smallest weighing 2.9 kg. Cannulation failed in 19 (7.8 %). The main indication in infants was suspicion of biliary atresia (n = 38). Six of the procedures (10.7 %) were therapeutic. In children the main indications were biliary stricture (n = 64) and investigation of primary sclerosing cholangitis (PSC) (n = 45). 119 (63.2 %) of these procedures were therapeutic.Complications were uncommon in infants; only two episodes of infection were registered. In children (> 1 year) post-ERCP pancreatitis were seen in 10.4 %. Conclusions Our retrospective series of ERCP procedures includes 56 procedures in infants, which is one of the largest series presented. Complications in infants are rare and post-ERCP pancreatitis was not seen. In older children 10.4 % experienced post-ERCP pancreatitis. In expert hands, ERCP was shown to be acceptably feasible and safe in infants and children.

CONTACT-TYPE DELAYED HYPERSENSITIVITY IN INFANTS AND CHILDREN: INDUCTION OF RHUS SENSITIVITY

PEDIATRICS ◽  
1961 ◽  
Vol 27 (1) ◽  
pp. 51-53
Author(s):  
William L. Epstein
Keyword(s):  
Intermediate Position ◽  
Infants And Children ◽  
Delayed Hypersensitivity ◽  
Older Children ◽  
Contact Sensitization ◽  
Contact Type ◽  
Frequency Of Contact ◽  
In Infants And Children

The frequency of contact sensitization to a Rhus allergen, pentadecyl catechol, was determined in 102 infants and children 1 month to 8 years of age. Children between 3 and 8 years were readily sensitized and showed a depth of sensitivity and intensity of reaction comparable to that seen in adults. Infants below the age of 1 year had a markedly depressed ability to react to Rhus allergens. Children between 1 and 3 years old assumed an intermediate position, being more reactive than infants, but less so than older children. Theoretically these observations suggest that the mechanism of delayed hypersensitivity matures more slowly than other processes of immunity and resistance. Clinically the findings mean that lack of exposure is a more important factor than lack of susceptibility in explaining the diminished incidence of clinical Rhus sensitivity in children below the age of 8 years.

Pharmacokinetics of Rapacuronium in Infants and Children with Intravenous and Intramuscular Administration

2000 ◽  
Vol 92 (2) ◽  
pp. 376-376 ◽  
Author(s):  
Lynne M. Reynolds ◽  
Andrew Infosino ◽  
Ronald Brown ◽  
Jim Hsu ◽  
Dennis M. Fisher
Keyword(s):  
Plasma Concentration ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Pediatric Anesthesia ◽  
Infants And Children ◽  
Intramuscular Administration ◽  
Pharmacokinetic Analysis ◽  
Intravenous Route ◽  
Population Pharmacokinetic ◽  
In Infants And Children

Background A nondepolarizing muscle relaxant with an onset and offset profile similar to succinylcholine is desirable for pediatric anesthesia. The onset and offset of rapacuronium are rapid in children. In the current study, the authors determined its pharmacokinetic characteristics in children. In addition to administering rapacuronium by the usual intravenous route, the authors also gave rapacuronium intramuscularly to determine uptake characteristics and bioavailability. Methods Forty unpremedicated patients aged 2 months to 3 yr were anesthetized with halothane, 0.82-1.0% end-tidal concentration. When anesthetic conditions were stable, rapacuronium was injected either into a peripheral vein (2 mg/kg for infants, 3 mg/kg for children) or a deltoid muscle (2.8 mg/kg for infants, 4.8 mg/kg for children). Four venous plasma samples were obtained from each subject 2-240 min after rapacuronium administration. A mixed-effects population pharmacokinetic analysis was applied to these values to determine bioavailability, absorption rate constant, and time to peak plasma concentration with intramuscular administration. Results Plasma clearance was 4.77 ml x kg(-1) x min(-1) + 8.48 ml/min. Intramuscular bioavailability averaged 56%. Absorption from the intramuscular depot had two rate constants: 0.0491 min(-1) (72.4% of absorbed drug) and 0.0110 min(-1) (27.6% of the absorbed drug). Simulation indicated that plasma concentration peaks 4.0 and 5.0 min after intramuscular rapacuronium in infants and children, respectively, and that, at 30 min, less than 25% of the administered dose remains to be absorbed from the intramuscular depot. Conclusions In infants and children, rapacuronium's clearance and steady state distribution volume are less than in adults. After intramuscular administration, bioavailability is 56%, and plasma rapacuronium concentrations peak within 4 or 5 min.

scholarly journals Optimal Dosing of Ceftriaxone in Infants Based on a Developmental Population Pharmacokinetic-Pharmacodynamic Analysis

2020 ◽  
Vol 64 (11) ◽  
Author(s):  
Ya-Kun Wang ◽  
Yue-E Wu ◽  
Xue Li ◽  
Li-Yuan Tian ◽  
Muhammad Wasim Khan ◽  
...  
Keyword(s):  
Population Pharmacokinetics ◽  
Sampling Strategy ◽  
Optimal Dose ◽  
Community Acquired Pneumonia ◽  
Pharmacokinetic Analysis ◽  
Population Pharmacokinetic ◽  
Evidence Based ◽  
Open Label ◽  
Large Variability ◽  
Pharmacodynamic Analysis

ABSTRACT Ceftriaxone is a third-generation cephalosporin used to treat infants with community-acquired pneumonia. Currently, there is a large variability in the amount of ceftriaxone used for this purpose in this particular age group, and an evidence-based optimal dose is still unavailable. Therefore, we investigated the population pharmacokinetics of ceftriaxone in infants and performed a developmental pharmacokinetic-pharmacodynamic analysis to determine the optimal dose of ceftriaxone for the treatment of infants with community-acquired pneumonia. A prospective, open-label pharmacokinetic study of ceftriaxone was conducted in infants (between 1 month and 2 years of age), adopting an opportunistic sampling strategy to collect blood samples and applying high-performance liquid chromatography to quantify ceftriaxone concentrations. Developmental population pharmacokinetic-pharmacodynamic analysis was conducted using nonlinear mixed effects modeling (NONMEM) software. Sixty-six infants were included, and 169 samples were available for pharmacokinetic analysis. A one-compartment model with first-order elimination matched the data best. Covariate analysis elucidated that age and weight significantly affected ceftriaxone pharmacokinetics. According to the results of a Monte Carlo simulation, with a pharmacokinetic-pharmacodynamic target of a free drug concentration above the MIC during 70% of the dosing interval (70% fT>MIC), regimens of 20 mg/kg of body weight twice daily for infants under 1 year of age and 30 mg/kg twice daily for those older than 1 year of age were suggested. The population pharmacokinetics of ceftriaxone were established in infants, and evidence-based dosing regimens for community-acquired pneumonia were suggested based on developmental pharmacokinetics-pharmacodynamics.

Intramuscular Rapacuronium in Infants and Children 

1999 ◽  
Vol 91 (5) ◽  
pp. 1285-1285 ◽  
Author(s):  
Lynne M. Reynolds ◽  
Andrew Infosino ◽  
Ronald Brown ◽  
James Hsu ◽  
Dennis M. Fisher
Keyword(s):  
Tracheal Intubation ◽  
Pediatric Patients ◽  
Minute Ventilation ◽  
Optimal Dose ◽  
Deltoid Muscle ◽  
Rapid Onset ◽  
Infants And Children ◽  
Halothane Anesthesia ◽  
Duration Of Action ◽  
In Infants And Children

Background Intravenous rapacuronium's rapid onset and short duration suggest that intramuscular rapacuronium might facilitate tracheal intubation without prolonged paralysis. Accordingly, the authors injected rapacuronium into the deltoid muscle to determine the optimal dose and time for intubation in pediatric patients. Methods Unpremedicated patients (aged, 2 months to 3 yr) were studied. Part I: Spontaneous minute ventilation (V(E)) and twitch tension were measured during N2O/halothane anesthesia. Rapacuronium (2.2-5.5 mg/kg, given intramuscularly, n = 23), succinylcholine (4 mg/kg, given intramuscularly, n = 12), or vecuronium (0.1 mg/kg, given intravenously, n = 15) was given. Time to 50% depression of V(E) and 10% recovery of twitch were measured. Dose for each patient was changed 10-20% according to the previous patient's response. Part II: In 22 patients anesthetized with 0.82-1.0% halothane, the optimal rapacuronium dose determined in part I (infants, 2.8 mg/kg; children, 4.8 mg/kg) was given intramuscularly. Laryngoscopy was scored. Time to laryngoscopy was increased or decreased 0.5 min according to the previous patient's response. Results Part I: Rapacuronium typically depressed ventilation in &lt; or = 2 min with 10% twitch recovery in 20-60 min. With succinylcholine, median time to ventilatory depression was 1.3 and 1.1 min for infants and children, respectively; for vecuronium, 0.7 and 0.6 min. Part I: Intubating conditions were good-excellent at 3.0 and 2.5 min in infants and children, respectively; time to 10% twitch recovery (mean +/- SD) was 31 +/- 14 and 36 +/- 14 min in the two groups. Conclusions This pilot study indicates that deltoid injection of rapacuronium, 2.8 mg/kg in infants and 4.8 mg/kg in children, permits tracheal intubation within 2.5-3.0 min, despite a light plane of anesthesia. Duration of action is intermediate.

scholarly journals Population Pharmacokinetic Modelling and Simulation to Determine the Optimal Dose of Nanoparticulated Sorafenib to the Reference Sorafenib

Pharmaceutics ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 629
Author(s):  
Ki Young Huh ◽  
Sejung Hwang ◽  
Sang Yeob Park ◽  
Hye Jung Lim ◽  
Miryung Jin ◽  
...  
Keyword(s):  
Compartmental Analysis ◽  
Optimal Dose ◽  
Compartment Model ◽  
Population Pharmacokinetic ◽  
Open Label ◽  
Post Dose ◽  
Multikinase Inhibitor ◽  
Final Model ◽  
Fasted State ◽  
Second Period

Sorafenib, an oral multikinase inhibitor, exhibits a highly variable absorption profile due to enterohepatic reabsorption and poor solubility. SYO-1644 improved the solubility of sorafenib by nanoparticulation technology leading to enhanced bioavailability. To evaluate the pharmacokinetically equivalent dose of SYO-1644 to the reference Nexavar® 200 mg, a randomized, open-label, replicated two-period study was conducted in healthy volunteers. A total of 32 subjects orally received a single dose of the following assigned treatment under a fasted state in the first period and repeated once more in the second period with a two-week washout: SYO-1644 100, 150 and 200 mg and Nexavar® 200 mg. Pharmacokinetic (PK) samples were collected up to 168 h post-dose. The PK profile was evaluated by both non-compartmental analysis and population PK method. With the final model, 2 × 2 crossover trial scenarios with Nexavar® 200 mg and each dose of SYO-1644 ranging from 100 to 150 mg were repeated 500 times by Monte Carlo simulation, and the proportion of bioequivalence achievement was assessed. Transit absorption compartments, followed by a one-compartment model with first-order elimination and enterohepatic reabsorption components were selected as the final model. The simulation results demonstrated that the SYO-1644 dose between 120 and 125 mg could yielded the highest proportion of bioequivalence.

Pediatric Pain

2019 ◽  
pp. 773-782
Author(s):  
Juliana H. O’Brien ◽  
Maggie C. Root
Keyword(s):  
Pain Management ◽  
Pain Assessment ◽  
Developmental Stages ◽  
Developmentally Appropriate ◽  
Infants And Children ◽  
Psychological Consequences ◽  
Older Children ◽  
Nonverbal Children ◽  
In Infants And Children ◽  
Experience Pain

Children and infants experience pain as a serious complication of disease and injury, but only recently have clinicians come to understand how children experience pain. Exposure to painful injury is associated with psychological consequences in infants and children, including posttraumatic stress symptoms, neurodevelopmental issues, increased anxiety, and cortical dysfunction in childhood. In seriously ill infants, pain may be associated with increased morbidity and mortality; in older children, untreated pain can lead to decreased functioning, social isolation, sleep disorders, and mood changes. Prevention and relief of pain for this vulnerable population is essential. Pain assessment and management in infants and children require that palliative care nurses understand the developmental stages of childhood. This chapter provides a recommended approach to pain assessment and pain management in children. It outlines age-specific and developmentally appropriate pain assessment tools. It describes commonly observed pain behaviors in verbal and nonverbal children. It highlights the management differences between acute pain, neuropathic pain, and chronic pain. It details a combined nonpharmacologic and pharmacologic (including weight-based dosing) approach for pain management.

Thrombosis in Infants and Children

Hematology ◽  
2006 ◽  
Vol 2006 (1) ◽  
pp. 86-96 ◽  
Author(s):  
Reinhard Schneppenheim ◽  
Jeanette Greiner
Keyword(s):  
Risk Factors ◽  
Clinical Presentation ◽  
Infants And Children ◽  
Therapeutic Interventions ◽  
Older Children ◽  
Thrombotic Risk ◽  
Therapeutic Decisions ◽  
Prophylactic Anticoagulation ◽  
Clinical Conditions ◽  
In Infants And Children

Abstract During the last decade much progress has been made toward better understanding of the underlying reasons causing thromboembolism in children. A considerable number of acquired and hereditary thrombotic risk factors have been identified which may also have an impact on therapeutic decisions and prognosis concerning outcome and the risk of a second event. However, indications for therapeutic interventions, such as thrombolysis and prophylactic anticoagulation with respect to the different clinical conditions and their combination with other risk factors, are not yet well defined. The following article describes the causes, clinical presentation and management of thrombosis in neonates, infants and older children, focusing on the clinically most relevant conditions.

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