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Paediatric Dose (paediatric + dose)
Selected AbstractsDosage regimens for inhaled therapy in children should be reconsideredJOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 2 2002JH Wildhaber Abstract: In current asthma guidelines, dosage regimens for inhalation therapy in children are based on adult doses and are generally titrated per kilogram of bodyweight or per square metre of body surface area. However, these recommendations do not correspond well with current knowledge of aerosol therapy in childhood. Lung deposition of the aerosolised drug is the key determinant for clinical efficacy and for systemic side effects of inhalation therapy. Lung deposition increases with age, whereas lung deposition expressed as a percentage per kilogram bodyweight is age-independent. This finding is explained by the self-regulating effect of age-dependent airway anatomy on lung deposition. Therefore, it is more likely that adult doses translate into paediatric doses only by virtue of the differences in self-limiting pulmonary deposition when using the same absolute nominal doses of the medication. Adapting the adult dose to a paediatric dose calculated on body size might be unnecessary and could lead to insufficient pulmonary deposition of medication. These findings suggest that dosage regimens for inhalation therapy for children may have to be reconsidered, and should be determined from dose-ranging studies rather than calculated from adult doses based on body size. [source] A pharmacokinetic study of piroxicam in children,ANAESTHESIA, Issue 10 2004P. Dix Summary Feldene MeltTM (piroxicam) is commonly used for analgesia following day case surgery. The manufacturer's recommended paediatric dose is 0.4 mg.kg,1 once daily. In children, plasma piroxicam levels of 3,5 ,g.ml,1 are associated with effective analgesia. However, in adults a single dose of 20 mg piroxicam (0.4 mg.kg,1 for a 50-kg adult) produces plasma levels of only 1.5,2.2 ,g.ml,1. We therefore studied plasma levels achieved by 0.4 mg.kg,1 or 1.0 mg.kg,1 piroxicam in 22 children aged between 3 and 16 years, undergoing elective orthopaedic surgery, in order to investigate the adequacy of single dosing. The first 12 patients received 0.4 mg.kg,1 Feldene MeltTM pre-operatively. Following assay of plasma piroxicam levels, a further 10 patients received 1.0 mg.kg,1 Feldene MeltTM. In both groups, five blood samples were taken at 2-hourly intervals. The mean (95% CI) piroxicam level following 0.4 mg.kg,1 was 2.90 (2.33,3.54) ,g.ml,1, compared to 5.87 (4.58,7.16) ,g.ml,1 following 1.0 mg.kg,1 (p = 0.0003). [source] Population pharmacokinetics of oral diclofenac for acute pain in childrenBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 6 2008Joseph F. Standing WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT , Diclofenac is an effective oral analgesic for acute postoperative pain. In adults 25 mg is half as effective as 50 mg, but 50 mg and 100 mg are similarly effective (ceiling effect). Diclofenac has linear pharmacokinetics in this range. , Diclofenac is frequently used ,off-label' in children for acute pain but optimum dosing is unclear (dosing of diclofenac in clinical paediatric studies ranges from 0.5,2.5 mg kg,1). There is currently no licensed oral paediatric formulation of diclofenac. WHAT THIS STUDY ADDS , Using a new diclofenac oral suspension, a dose of 1 mg kg,1 in children aged 1 to 12 years gives a similar exposure to 50 mg in adults; paediatric patients are unlikely to benefit from higher doses. AIMS To develop a population pharmacokinetic model for a new diclofenac suspension (50 mg 5 ml,1) in adult volunteers and paediatric patients, and recommend a dose for acute pain in children. METHODS Blood samples were drawn at the start and end of surgery, and on removal of the venous cannula from 70 children (aged 1 to 12 years, weight 9 to 37 kg) who received a preoperative oral 1 mg kg,1 dose; these were pooled with rich (14 post-dose samples) data from 30 adult volunteers. Population pharmacokinetic modelling was undertaken with NONMEM. The optimum adult dose of diclofenac for acute pain is 50 mg. Simulation from the final model was performed to predict a paediatric dose to achieve a similar AUC to 50 mg in adults. RESULTS A total of 558 serum diclofenac concentrations from 100 subjects was used in the pooled analysis. A single disposition compartment model with first order elimination and dual absorption compartments was used. The estimates of CL/F and VD/F were 53.98 l h,1 70 kg,1 and 4.84 l 70 kg,1 respectively. Allometric size models appeared to predict adequately changes in CL and VD with age. Of the simulated doses investigated, 1 mg kg,1 gave paediatric AUC(0,12 h) to adult 50 mg AUC(0,12 h) ratios of 1.00, 1.08 and 1.18 for ages 1,3, 4,6 and 7,12 years respectively. CONCLUSIONS This study has shown 1 mg kg,1 diclofenac to produce similar exposure in children aged 1 to 12 years as 50 mg in adults, and is acceptable for clinical practice; patients are unlikely to obtain further benefit from higher doses. [source] Desloratadine dose selection in children aged 6 months to 2 years: comparison of population pharmacokinetics between children and adultsBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 2 2007Samir K. Gupta What is already known about this subject ,,According to recent literature, the pathophysiologies of allergic rhinitis and chronic idiopathic urticaria are thought to be similar in adults and children. In addition, the response to antihistamine treatment is similar in adults and children, suggesting a similar concentration-response relationship. ,,However, an appropriate dose selection and the pharmacokinetics of desloratadine in children of ,6 months,,2 years old have never been addressed in the literature. What this study adds ,,This study demonstrated that desloratadine syrup offers a safe treatment option for allergic conditions in young children. ,,A suitable dose for children aged ,6 months,<1 year is 1.0 mg, while the corresponding predicted dose for children aged ,1 year,,2 years is 1.25 mg. These paediatric doses yielded similar systemic desloratadine exposures (AUC) to those seen with a typical adult dose of 5.0 mg. Aims The aim of this study was to identify the dose of desloratadine in children aged ,6 months,,2 years that would yield a single-dose target exposure (AUC) comparable with that in adults taking 5 mg desloratadine as syrup. Methods In a phase 1, single-dose, open-label, pharmacokinetic study in 58 children aged ,6 months,<1 year and ,1 year,,2 years were randomly assigned to desloratadine syrup 0.625 mg (1.25 ml) and 1.25 mg (2.5 ml), respectively. Because the volume of blood that could be collected from individual subjects was limited, a population pharmacokinetic approach was used to estimate the pharmacokinetics of desloratadine. Safety was assessed based on results of screening and postdose physical examinations, laboratory safety tests, vital signs, and adverse events. Results The apparent clearance (CL/F) of desloratadine, population estimate (%CV), in children aged ,6 months,<1 year was 27.8 l h,1 (35) and corresponding values in children ,1 year,,2 years was 35.5 l h,1 (51), compared with 137 l h,1 (58) for adults. The CL/F ratios (children to adults) indicated that doses of 1 mg for ,6 months,<1 year and 1.25 mg for ,1 year,,2 years would result in similar systemic exposure to that observed in adults receiving the recommended 5 mg dose. Desloratadine was well tolerated with no safety issues. Conclusions Doses of 1.0 and 1.25 mg in children aged ,6 months,,2 years should result in an exposure to desloratadine similar to that of adults receiving doses of 5 mg. [source] Age-related differences in the pharmacokinetics of stavudine in 272 children from birth to 16 years: a population analysisBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 1 2007V. Jullien Aims To develop a population pharmacokinetic model for stavudine in children and to investigate the consistency of the currently recommended dose based on adult target concentrations. Methods The pharmacokinetics of stavudine were investigated using a population approach. Individual estimates of CL/F were used to calculate the stavudine dose required to achieve the area under the concentration-time curve reported in adults given recommended doses. Results Stavudine pharmacokinetics were well described by a one-compartment model with zero-order absorption. Typical population estimates (% interindividual variability) of the apparent distribution volume (V/F) and plasma clearance (CL/F) were 40.9 l (32%) and 16.5 l h,1 (38%), respectively. Stavudine V/F and CL/F were similarly related to age. Mean calculated doses (0.61 mg kg,1 for children less than 2 weeks, 1.23 mg kg,1 for children more than 2 weeks with bodyweight less than 30 kg, and 31.5 mg for children with a bodyweight between 30 and 60 kg) were in agreement with the current paediatric doses (0.5 mg kg,1, 1 mg kg,1, and 30 mg, respectively). Conclusions Our findings support the current recommended paediatric dosage regimens for stavudine, as they result in the same exposure to the drug as in adults. [source] | ||||||||||