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Background: Long term treatment of pediatric patients with oral anticancer drugs (OADs) requires the parents/caregivers to prepare the drug at home. The handling procedures in the home setting are, however, not regulated by Swedish law and the parents are often left without guidance on how to handle OADs in a safe way. Aim: The aim of this study was to increase understanding of how OADs are handled by parents/caregivers in the home setting before and after an intervention. Methods: Parents of pediatric cancer patients were observed and videotaped during their handling of OADs in the home setting before and after the intervention. During the intervention, the parents were provided with written instructions, movie clips and practical training on handling the OADs. Four checklists were used to compare and score the four handling procedures (measuring an oral suspension, cutting tablets, dissolving tablets, and opening capsules) for each parent before and after the intervention. Results: The intervention significantly improved the OAD handling procedures among the studied parents. The median score for correct handling was 19% (IQR: 3.6 to 30%) before the intervention and 89.5% (IQR: 71.5 to 94.5%) after the intervention (p < 0.0001). Conclusions: An intervention comprising practical training and information presented in different forms improved the handling of OADs at home by parents. There is an urgent need to implement this method in all oncology centers in Sweden, educate HCPs to standardize the presentation of information. There is also a great need to provide parents with age-appropriate oral drug formulations from the local hospital pharmacies in Sweden. [ABSTRACT FROM AUTHOR]

Background: Naloxone has a high affinity for the µ‐opioid receptor and acts as a competitive antagonist, thus reversing the effects of opioids. Naloxone is often administrated intravenously, but there is a growing interest in the intranasal route in treating patients with opioid overdose, and in reversing effects after therapeutic use of opioids. As administration is painless and no intravenous access is needed, the intranasal route is especially useful in children. Aim: The aim of this study was to investigate the uptake of naloxone 0.4 mg/ml during the first 20 min after administration as a nasal spray in a pediatric population, with special focus on the time to achieve maximum plasma concentration. Methods: Twenty children, 6 months–10 years, were included in the study. The naloxone dose administered was 20 µg/kg, maximum 0.4 mg, divided into repeated doses of 0.1 ml in each nostril. Venous blood samples were collected at 5, 10, and 20 min after the end of administration. Results: All patients had quantifiable concentrations of naloxone in venous blood at 5 min, and within 20 min, peak concentration had been reached in more than half of the children. At 20 min after intranasal administration, the plasma naloxone concentrations were within the range of 2–6 nanogram/ml. Conclusion: This study confirms the clinical experience that the rapid effect of naloxone after intranasal administration in children was reflected in rapid systemic uptake to achieve higher peak plasma concentrations than previously reported in adults. [ABSTRACT FROM AUTHOR]

Oral clonidine is used as premedication in children. The bioavailability of clonidine given orally in adults is 75-100% but is unknown in children. Children (3-10 years) undergoing adenotonsillectomy were administered oral clonidine 4 mcg·kg mixed with apple fruit drink as premedication. Intravenous plasma was assayed for clonidine concentration at 5, 15, 30, 45 min and 1, 2, 4, 6, 12, 18 h after administration. Clonidine plasma concentrations were determined by liquid chromatography-mass spectroscopy, and pharmacokinetic parameters were calculated using nonlinear effects mixed-effects models. Current data were pooled with published time-concentration profiles from children ( n = 49) administered intravenous clonidine to determine oral bioavailability. There were eight children studied (age 3-10 years, weight 10.5-36 kg). A two-compartment model with first-order absorption and elimination was used to describe time-concentration profiles. Population parameter estimates (CV%; 95% CI), standardized to a 70-kg person, were absorption half-life (Tabs), 0.45 (85.1; 0.221-0.884) h, absorption lag time (Tlag), 0.148 (91.2; 0.002-0.316) h, Clearance (CL) 17.9 (30.3; 16-20.3) l·h per 70 kg, between compartment clearance (Q) 121 (44.3; 80.1-165) l·h per 70 kg, central volume (V1) 81.2 (71.5; 60.7-105) l·70 kg, peripheral volume of distribution (V2) 113 (33.9; 91-131) l·70 kg. The oral bioavailability was 55.4% (CV 6.4%; 95% CI 0.469, 0.654). Clonidine administered with an apple fruit drink displays a variable and relatively slow absorption after oral administration ( T 1.04 h, C 0.77 mcg·l). The oral bioavailability was 55.4%, which is less than reported in adults. Consequently, higher oral doses of clonidine (per kg) are required when this formulation is used to achieve concentrations similar to those reported in adults. [ABSTRACT FROM AUTHOR]

The aim of this prospective, age-stratified, observational study was to determine the cranial extent of spread of a large volume (1.5 ml·kg, ropivacaine 0.2%), single-shot caudal epidural injection using real-time ultrasonography. Fifty ASA I-III children were included in the study, stratified in three age groups; neonates, infants (1-12 months), and toddlers (1-4 years). The caudal blocks were performed during ultrasonographic observation of the spread of local anesthetic (LA) in the epidural space. A significant inverse relationship was found between age, weight, and height, and the maximal cranial level reached by 1.5 ml·kg of LA. In neonates, 93% of the blocks reached a cranial level of ≥Th12 vs 73% and 25% in infants and toddlers, respectively. Based on our data, a predictive equation of segmental spread was generated: Dose (ml/spinal segment) = 0.1539·(BW in kg)-0.0937. This study found an inverse relationship between age, weight, and height and the number of segments covered by a caudal injection of 1.5 ml·kg of ropivacaine 0.2% in children 0-4 years of age. However, the cranial spread of local anesthetics within the spinal canal as assessed by immediate ultrasound visualization was found to be in poor agreement with previously published predictive equations that are based on actual cutaneous dermatomal testing. [ABSTRACT FROM AUTHOR]

Background: The α2 agonist clonidine has become a popular drug for premedication in children. Effects and pharmacokinetics after oral, rectal, and intravenous administration are well known. The aim of this study was to investigate the absorption pharmacokinetics of clonidine nasal drops in children. Methods: Thirteen ASA I pediatric patients received after induction of anesthesia 4 mcg·kg−1 of clonidine by the nasal route. Blood samples were taken during a 12-h period and plasma levels of clonidine were analyzed by liquid chromatography–mass spectrometry. Data were calculated by a computer-aided curve-fitting program. Results: Plasma pharmacokinetics following administration of clonidine nasal drops showed a considerable interindividual variability and absorption was delayed and limited. A total of 95% confidence intervals for maximum plasma concentration and time to achieve maximum plasma concentration were 0.4–0.6 ng·ml−1 and 1.4–3.0 h, respectively. Conclusions: Clonidine nasal drops are erratically absorbed from the nasal mucosa and, thus, this mode of drug administration is not recommended for premedication purposes. [ABSTRACT FROM AUTHOR]

Background: There are few data describing clonidine population pharmacokinetics in children (0–15 years) despite common use. Current pediatric data, described in terms of elimination half-life or Cmax and Tmax, poorly explain variability in drug responses among individuals representative of those in whom the drug will be used clinically. Methods: Published data from four studies investigating clonidine PK after intravenous (i.v.), rectal and epidural administration ( n = 42) were combined with an open-label study undertaken to examine the pharmacokinetics of i.v. clonidine 1–2 μg·kg−1 bolus in children after cardiac surgery ( n = 41). A population pharmacokinetic analysis of clonidine time–concentration profiles (380 observations) was undertaken using nonlinear mixed effects modeling. Estimates were standardized to a 70-kg adult using allometric size models. Results: Children had a mean age of 4 (sd 3.6 years, range 1 week–14 years) years and weight 17.8 (sd 12.6, range 2.8–60) kg. A two compartment disposition model with first-order elimination was superior to a one compartment model. Population parameter estimates (between subject variability) were clearance (CL) 14.6 (CV 35.1%) l·h−1 70 kg−1, central volume of distribution (V1) 62.5 (71.1%) l 70 kg−1, intercompartment clearance (Q) 157 (77.3%) l·h−1 70 kg−1 and peripheral volume of distribution (V2) 119 (22.9%) l 70 kg−1. Clearance at birth was 3.8 l·h−1 70 kg−1 and matured with a half-time of 25.7 weeks to reach 82% adult rate by 1 year of age. The volumes of distribution, but not clearance, were increased after cardiac surgery (V1 123%, V2 126%). There was a lag time of 2.3 (CV 73.2%) min before absorption began in the rectum. The absorption half-life from the epidural space was slower than that from the rectum (0.98 CV 24.5% h vs 0.26 CV 32.3% h). The relative bioavailability of epidural and rectal clonidine was unity ( F = 1). Conclusions: Clearance in neonates is approximately one-third that described in adults, consistent with immature elimination pathways. Maintenance dosing, which is a function of clearance, should be reduced in neonates and infants when using a target concentration approach. [ABSTRACT FROM AUTHOR]

This case report presents the pharmacokinetics of doxorubicin and etoposide in a 14-year-old morbidly obese (body mass index: 46.3 kg/m2) male patient with Hodgkin disease. Dosing based on an adjusted body surface area resulted in a dose reduction by approximately 25% as compared to dosing based on actual body surface area. Plasma clearance of doxorubicin as well as plasma clearance and elimination rate of etoposide for this patient was comparable to pharmacokinetic data from nonobese pediatric patients. The therapy was well tolerated without any specific toxicity and a complete response was obtained after 2 scheduled courses, with the patient in complete remission 25 months after end of treatment. [ABSTRACT FROM AUTHOR]

Background: High-volume (1.5 ml kg-1) caudal block in infants results in major reductions of cerebral blood flow velocity (CBFV) and cerebral oxygenation, caused by rostral CSF movement which increases intracranial pressure. The primary aim of this study was to determine the relationship between injected volume and CBFV changes. We hypothesised that this volume-blood flow relationship would have a similar albeit inverted shape to the well-known intracranial pressure volume-pressure curve.Methods: Fifteen subjects, age 0-6 months, mean (range) weight 4.9 (2.1-6.4) kg, were studied. A 1.5 ml kg-1 caudal injection of 0.2% ropivacaine was administered in three phases separated by two pauses. Subjects were randomised into five groups, in whom the pauses were implemented at different pre-set proportions of the total injected volume. Middle cerebral artery Doppler ultrasonography was used for CBFV measurements (Vmax, peak CBF velocity; Vmin, lowest CBF velocity; velocity time index). Mean flow velocity, pulsatility index, and resistivity index were calculated, and haemodynamic parameters were recorded.Results: CBFV parameters decreased in all patients. The most affected parameter, Vmin, was reduced by ∼50% (range 15-68%) compared with baseline. There was a nonlinear relationship between the volume of the first phase injection and the CBFV measurement during the first pause. Across all time points, there was a linear relationship between volume administered and CBFV. Systemic haemodynamic parameters remained stable throughout the study.Conclusions: Injection pauses appear to attenuate adverse CBFV increases during administration of a high-volume caudal block. [ABSTRACT FROM AUTHOR]

Summary In previous studies, we observed that lactate concentrations in interstitial white adipose tissue are higher in small infants than in adults. Moreover, no lipolysis following catecholamine challenge has been reported in neonates and small infants. Our aim was to determine with microdialysis whether the above mentioned age-dependent changes could be detected in situ after surgery. A microdialysis catheter was introduced into the abdominal subcutaneous tissue in 13 neonates and 12 children undergoing surgery. Interstitial concentrations of glucose, lactate and glycerol were measured hourly during the first 20 postoperative hours. The concentrations of lactate in interstitial white adipose tissue were consistently higher in neonates compared to older children, with a significant difference during the 9–18 h postoperative period (P < 0.05). A significant difference in the lactate:glucose ratio was observed at 1–2, 8–10, 15 and 18 h postoperatively (P < 0.05). No significant differences were observed between the two groups with respect to glycerol and glucose concentrations. Interstitial lactate concentrations in white adipose tissue were higher in neonates compared with children in the early postoperative period. No age-dependent difference in postoperative lipolysis, measured as interstitial glycerol concentrations, was observed. Thus, an age-dependent difference in interstitial lactate production, but not lipolysis, was detected in the early postoperative period. [ABSTRACT FROM AUTHOR]