Aim: To develop an HPLC method to quantify midazolam in a new oral formulation for pediatric use. Methods: The stability of the new formulation was evaluated at different storage conditions and a preliminary assay of ...Aim: To develop an HPLC method to quantify midazolam in a new oral formulation for pediatric use. Methods: The stability of the new formulation was evaluated at different storage conditions and a preliminary assay of relative bioavailability was carried out in healthy volunteers. Results: The method of quantification was linear in the range of 5 to 60 μg·mL-1. The midazolam amount in the formulation remained stable for 90 days at 4 and 40℃ (in the dark) while at 25℃ was stable only for 14 days (exposed to light). Discussion: The relative bioavailability assay suggests that our preparation of midazolam in white chocolate reaches plasma levels similar to those induced by the apple juice formulation. Conclusion: This new white chocolate formulation masks the unpleasing flavour and has a more attractive presentation to the paediatric patient, which may be useful for children sedation and to ease its management by health carers.展开更多
Background:Recently,sildenafil was introduced to treat pulmonary arterial hypertension (PAH);however,there are currently few studies on the pharmacokinetics of sildenalfil in children.Therefore,we aimed to carry out a...Background:Recently,sildenafil was introduced to treat pulmonary arterial hypertension (PAH);however,there are currently few studies on the pharmacokinetics of sildenalfil in children.Therefore,we aimed to carry out a pharmacokinetic study of sildenafil in children with PAH using a single dose.Methods:Twelve children diagnosed with PAH,consisting of with ten males and two females,were recruited for the study after obtaining written consent from their parents or guardians.Blood samples were obtained predose and at 0.25,0.5,1,2,4,8 and 12 hours after the oral administration of 1 mg/kg of sildenafil using an extemporal pediatric formulation developed in our laboratory.The samples were analyzed using a previously validated high performance liquid chromatography method.Results:A pharmacokinetic analysis using the WinNonlin 3.1 program that considered the Akaike information criterion (AIC) for sdecting a more adjustable model was performed.The following pharmacokinetic parameters were obtained:maximal concentration (Cmax):366+179 ng/mL,time to maximal concentration:0.92±0.30 hours,elimination half-life (t1/2):2.41±1.18 hours,total clearance (CLto/F):5.85±2.81 L/hour,volume of distribution (Vd/F):20.13±14.5 L,absorption rate constants (Ka):0.343 hour-1,elimination rate (Ke):0.35 hour-1,area under curve from zero to infinity:2061±618 ng/mL/hour.The data of all patients adjusted to the model of one compartment were corroborated using AIC.Conclusions:The parameters Ka,Ke and t1/2 were found to be similar to those reported in adults;however,the values of Cmax and Vd/F were significantly higher.Based on these findings,we propose that treatment regimen of sildenafil be adjusted in children with PAH.展开更多
文摘Aim: To develop an HPLC method to quantify midazolam in a new oral formulation for pediatric use. Methods: The stability of the new formulation was evaluated at different storage conditions and a preliminary assay of relative bioavailability was carried out in healthy volunteers. Results: The method of quantification was linear in the range of 5 to 60 μg·mL-1. The midazolam amount in the formulation remained stable for 90 days at 4 and 40℃ (in the dark) while at 25℃ was stable only for 14 days (exposed to light). Discussion: The relative bioavailability assay suggests that our preparation of midazolam in white chocolate reaches plasma levels similar to those induced by the apple juice formulation. Conclusion: This new white chocolate formulation masks the unpleasing flavour and has a more attractive presentation to the paediatric patient, which may be useful for children sedation and to ease its management by health carers.
文摘Background:Recently,sildenafil was introduced to treat pulmonary arterial hypertension (PAH);however,there are currently few studies on the pharmacokinetics of sildenalfil in children.Therefore,we aimed to carry out a pharmacokinetic study of sildenafil in children with PAH using a single dose.Methods:Twelve children diagnosed with PAH,consisting of with ten males and two females,were recruited for the study after obtaining written consent from their parents or guardians.Blood samples were obtained predose and at 0.25,0.5,1,2,4,8 and 12 hours after the oral administration of 1 mg/kg of sildenafil using an extemporal pediatric formulation developed in our laboratory.The samples were analyzed using a previously validated high performance liquid chromatography method.Results:A pharmacokinetic analysis using the WinNonlin 3.1 program that considered the Akaike information criterion (AIC) for sdecting a more adjustable model was performed.The following pharmacokinetic parameters were obtained:maximal concentration (Cmax):366+179 ng/mL,time to maximal concentration:0.92±0.30 hours,elimination half-life (t1/2):2.41±1.18 hours,total clearance (CLto/F):5.85±2.81 L/hour,volume of distribution (Vd/F):20.13±14.5 L,absorption rate constants (Ka):0.343 hour-1,elimination rate (Ke):0.35 hour-1,area under curve from zero to infinity:2061±618 ng/mL/hour.The data of all patients adjusted to the model of one compartment were corroborated using AIC.Conclusions:The parameters Ka,Ke and t1/2 were found to be similar to those reported in adults;however,the values of Cmax and Vd/F were significantly higher.Based on these findings,we propose that treatment regimen of sildenafil be adjusted in children with PAH.
