Assessing circadian rhythms during prolonged midazolam infusion in the pediatric intensive care unit (PICU) children

Bienert, Agnieszka; Bartkowska-Śniatkowska, Alicja; Wiczling, Paweł; Rosada-Kurasińska, Jowita; Grześkowiak, Małgorzata; Żaba, Czesław; Tężyk, Artur; Sokołowska, Anna; Kaliszan, Roman; Grześkowiak, Edmund

doi:10.1016/s1734-1140(13)70969-1

Cited by 13 publications

(12 citation statements)

References 52 publications

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“…Therefore, the probability that children will actually engage in increased physical activity is likely higher than other approaches where participation is volitional (i.e., sports, after-school programs, etc.). The A + PAAC approach delivers academic lessons using physical activity, thus there is no reduction in academic instruction time; a desirable feature in the climate of No Child Left Behind of 2001 [45]. A + PAAC is minimal intervention that requires virtually no additional financial resources or time commitment to implement.…”

Section: Discussionmentioning

confidence: 99%

Physical activity and academic achievement across the curriculum (A + PAAC): rationale and design of a 3-year, cluster-randomized trial

et al. 2013

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BackgroundImproving academic achievement and reducing the rates of obesity in elementary school students are both of considerable interest. Increased physical activity during academic instruction time during school offers a potential intervention to address both issues. A program titled “Physical Activity Across the Curriculum” (PAAC) was developed in which classroom teachers in 22 elementary schools were trained to deliver academic instruction using physical activity with a primary aim of preventing increased BMI. A secondary analysis of data assessed the impact of PAAC on academic achievement using the Weschler Individual Achievement Test-II and significant improvements were shown for reading, math and spelling in students who participated in PAAC. Based on the results from PAAC, an adequately powered trial will be conducted to assess differences in academic achievement between intervention and control schools called, “Academic Achievement and Physical Activity Across the Curriculum (A + PAAC).”Methods/designSeventeen elementary schools were cluster randomized to A + PAAC or control for a 3-year trial. Classroom teachers were trained to deliver academic instruction through moderate-to-vigorous physical activity with a target of 100+ minutes of A + PAAC activities per week. The primary outcome measure is academic achievement measured by the Weschler Individual Achievement Test-III, which was administered at baseline (Fall 2011) and will be repeated in the spring of each year by assessors blinded to condition. Potential mediators of any association between A + PAAC and academic achievement will be examined on the same schedule and include changes in cognitive function, cardiovascular fitness, daily physical activity, BMI, and attention-to-task. An extensive process analysis will be conducted to document the fidelity of the intervention. School and student recruitment/randomization, teacher training, and baseline testing for A + PAAC have been completed. Nine schools were randomized to the intervention and 8 to control. A random sample of students in each school, stratified by gender and grade (A + PAAC = 370, Control = 317), was selected for outcome assessments from those who provided parental consent/child assent. Baseline data by intervention group are presented.DiscussionIf successful, the A + PAAC approach could be easily and inexpensively scaled and disseminated across elementary schools to improve both educational quality and health. Funding source: R01- DK85317. Trial registration: US NIH Clinical Trials, http://NCT01699295.

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Section: Discussionmentioning

confidence: 99%

Physical activity and academic achievement across the curriculum (A + PAAC): rationale and design of a 3-year, cluster-randomized trial

et al. 2013

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“…On the other hand, other studies have not found such a pattern . In a study conducted in children hospitalized in intensive care units, and with the use of population pharmacokinetics, the light–dark cycle was found to have no impact on CYP3A activity …”

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confidence: 91%

“…17,18 In a study conducted in children hospitalized in intensive care units, and with the use of population pharmacokinetics, the light-dark cycle was found to have no impact on CYP3A activity. 19 The primary objective of this prospective study was to test the existence of a circadian rhythm in the hepatic CYP3A activity, and quantify its magnitude. This will be achieved by developing a population pharmacokinetic model accounting for hepatic CYP3A mediated elimination based on plasma concentration profiles of midazolam and its main metabolite, 1-OH midazolam, 20 from a cohort of healthy volunteers given a continuous intravenous infusion of midazolam.…”

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confidence: 99%

Population pharmacokinetic analysis of circadian rhythms in hepatic CYP3A activity using midazolam

Tomalik-Scharte

Suleiman

Frechen

et al. 2014

The Journal of Clinical Pharmacology

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Diurnal changes in the activity of drug metabolizing enzymes may contribute to the variability in drug disposition and drug effects. The aim of this study was to quantify the circadian rhythmicity exhibited by hepatic CYP3A. A 10 μg/kg intravenous bolus dose, followed by a 30-hour 4 μg/kg/h intravenous infusion of midazolam, used as a probe substrate for hepatic CYP3A activity, was administered to 16 healthy volunteers (8 males and 8 females). Blood samples were drawn hourly for 24 hours after achieving steady state, and plasma concentrations of midazolam and its main metabolite 1-OH midazolam were determined. Population pharmacokinetic analysis was performed using nonlinear mixed effects modeling. One-compartment pharmacokinetic models best described midazolam and 1-OH midazolam pharmacokinetic disposition. An unequivocal but minor diurnal pattern was identified in the midazolam plasma concentration profiles, which was described using a cosine function with a 24-hours period. The fluctuation in the relative CYP3A activity ranged between 10% above average around 15:00, and 10% below average around 03:00. None of the covariates tested had a significant impact on the parameters estimated. Although a diurnal pattern in hepatic CYP3A activity was identified, its magnitude suggests that it is small and without clinical significance for drug therapy.

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“…Several chronopharmacokinetic studies on midazolam have been published 15–19. In most of these studies, however, midazolam was administered either orally18 or as an intravenous (i.v.)…”

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confidence: 99%

“…In most of these studies, however, midazolam was administered either orally18 or as an intravenous (i.v.) infusion,15,17,19 and therefore not all PK parameters (absorption rate constant, bioavailability, and clearance) could be assessed separately. To distinguish between bioavailability, systemic clearance, and volume of distribution, oral and i.v.…”

mentioning

confidence: 99%

Population Pharmacokinetic Model Characterizing 24‐Hour Variation in the Pharmacokinetics of Oral and Intravenous Midazolam in Healthy Volunteers

Rongen

Kervezee

Brill

et al. 2015

CPT Pharmacom & Syst Pharma

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Daily rhythms in physiology may affect the pharmacokinetics of a drug. The aim of this study was to evaluate 24-hour variation in the pharmacokinetics of the CYP3A substrate midazolam. Oral (2 mg) and intravenous (1 mg) midazolam was administered at six timepoints throughout the 24-hour period in 12 healthy volunteers. Oral bioavailability (population mean value [RSE%] of 0.28 (7.1%)) showed 24-hour variation that was best parameterized as a cosine function with an amplitude of 0.04 (17.3%) and a peak at 12:14 in the afternoon. The absorption rate constant was 1.41 (4.7%) times increased after drug administration at 14:00. Clearance (0.38 L/min (4.8%)) showed a minor 24-hour variation with an amplitude of 0.03 (14.8%) L/min and a peak at 18:50. Simulations show that dosing time minimally affects the concentration time profiles after intravenous administration, while concentrations are higher during the day compared to the night after oral dosing, reflecting considerable variation in intestinal processes.

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Assessing circadian rhythms during prolonged midazolam infusion in the pediatric intensive care unit (PICU) children

Cited by 13 publications

References 52 publications

Physical activity and academic achievement across the curriculum (A + PAAC): rationale and design of a 3-year, cluster-randomized trial

Physical activity and academic achievement across the curriculum (A + PAAC): rationale and design of a 3-year, cluster-randomized trial

Population pharmacokinetic analysis of circadian rhythms in hepatic CYP3A activity using midazolam

Population Pharmacokinetic Model Characterizing 24‐Hour Variation in the Pharmacokinetics of Oral and Intravenous Midazolam in Healthy Volunteers

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