Population pharmacokinetics of oral diclofenac for acute pain in children

Standing, Joseph F.; Howard, Richard; Johnson, Atholl; Savage, Imogen; Wong, Ian C. K.

doi:10.1111/j.1365-2125.2008.03289.x

Cited by 22 publications

(33 citation statements)

References 25 publications

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“…In the literature, both a fixed value of 0.75 [10][11][12] and an estimated value [13][14][15] for the allometric exponent have been reported for scaling clearance in children.…”

Section: Introductionmentioning

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 the literature, both a fixed value of 0.75 [10][11][12] and an estimated value [13][14][15] for the allometric exponent have been reported for scaling clearance in children.…”

Section: Introductionmentioning

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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“…A further eight patients recruited during a pilot of the case report form, and 71 patients taking part in a pharmacokinetic study of a new diclofenac oral suspension at Great Ormond Street Hospital [9], were also included for the analysis of adverse events. Table 2 gives the demographic details of the 385 patients recruited to the main adverse drug reaction study; 301 of these received diclofenac.…”

Section: Demographics and Diclofenac Utilizationmentioning

confidence: 99%

“…Adverse event data from the main, pilot and pharmacokinetic [9] studies were collected from 380 patients. A total of 224 adverse events were recorded in 130 patients, eight of which were unclassifiable (laboratory abnormalities with no temporal information) and 35 unrelated events that occurred before diclofenac was administered.…”

Section: Adverse Eventsmentioning

confidence: 99%

“…Adapted from: Edwards IR and Aronson JK, 2000 [13] dose of 1 mg kg -1 , which gives a similar exposure to 50 mg in adults [9]. While many patients in this study received a single dose, this reflects how diclofenac is used in practice, meaning the results should be relevant to health professionals treating children with acute pain.…”

Section: Figurementioning

confidence: 99%

“…This study formed part of an investigation to address the lack of information on diclofenac off-label use in children, which also included a pharmacokinetic study [9] and systematic literature review [10]. The aims of the present study were to ascertain the types of common (occurring in >1% of patients) adverse drug reactions caused by diclofenac in children treated for acute pain, and to report all serious adverse events regardless of their cause.…”

Section: Introductionmentioning

confidence: 99%

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Prospective observational study of adverse drug reactions to diclofenac in children

Standing

Ooi

Keady

et al. 2009

Brit J Clinical Pharma

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WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Diclofenac is frequently used off-label in children for acute pain, but little information is available on diclofenac adverse drug reactions in this population. WHAT THIS STUDY ADDS• The common adverse drug reactions of diclofenac for acute pain in children are of a similar type to those seen in adults.• Serious adverse reactions occur in <0.8% of children and the incidence of diclofenacinduced bronchospasm in asthmatic children is <2.7%. AIMThe aim of this study was to investigate the type of common (occurring in >1% of patients) adverse reactions caused by diclofenac when given to children for acute pain. METHODSA prospective observational study was undertaken on paediatric surgical patents aged Յ12 years at Great Ormond Street and University College London Hospitals. All adverse events were recorded, and causality assessment used to judge the likelihood of them being due to diclofenac. Prospective recruitment meant not all patients were prescribed diclofenac, allowing an analysis of utilization. Causality of all serious adverse events was reviewed by an expert panel. RESULTSChildren prescribed diclofenac were significantly older, and stayed in hospital for shorter periods than those who were not. Diclofenac was not avoided in asthmatic patients. Data on 380 children showed they suffer similar types of nonserious adverse reactions to adults. The incidence (95% confidence interval) of rash was 0.8% (0.016, 2.3); minor central nervous system disturbance 0.5% (0.06, 1.9); rectal irritation with suppositories 0.3% (0.009, 1.9); and diarrhoea 0.3% (0.007, 1.5). No serious adverse event was judged to be caused by diclofenac, meaning the incidence of serious adverse reactions to diclofenac in children is <0.8%. CONCLUSIONChildren given diclofenac for acute pain appeared to suffer similar types of adverse reactions to adults; the incidence of serious adverse reaction is <0.8%.

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Embryonic exposure to diclofenac disturbs actin organization and leads to myofibril misalignment

Chen

Chang

Wang

et al. 2011

Birth Defects Research Pt B

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The objective of this study was to investigate the embryotoxicity of diclofenac. Zebrafish (Danio rerio) embryos at 12 hpf were treated with different dosages of diclofenac (0-2,000 ppm) for different time courses (12-72 hr). Results showed no evident differences in survival rates or morphological changes between the mock-treated control (0 ppm) zebrafish embryos and those with 1-ppm diclofenac-exposure (12-24, 12-36 hpf). In contrast, after higher doses (5 and 10 ppm) of exposure, embryos displayed some defective phenotypes, including malformed somite boundary, a twisted body axis, and shorter body length. In addition, diclofenac-treated embryos exhibited significantly reduced frequencies of spontaneous in-chorion contractions in comparison with mock-control littermates (mock-control: 13.20 ± 2.24 vs. 5-10 ppm diclofenac: 6.66 ± 1.35-3.03 ± 1.84). Subtle changes were easily observed by staining with specific monoclonal antibodies F59 and phalloidin to detect morphological changes in muscle fibers and formation of F-actin, respectively. Our data show that diclofenac treatment disturbs actin organization and muscle fiber alignment, thus causing malformed somite phenotypes.

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Population pharmacokinetics of oral diclofenac for acute pain in children

Cited by 22 publications

References 25 publications

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

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

Prospective observational study of adverse drug reactions to diclofenac in children

Embryonic exposure to diclofenac disturbs actin organization and leads to myofibril misalignment

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