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Background: Genetic polymorphisms play an important role in the response to a drug regimen, based on the metabolic rate, which determines the interindividual variability. Quantitative differences in the cytochrome P450 expression, specially CYP2D6, can be assayed by means of a drug metabolism such as that of dextromethorphan. Aim: To characterize the oxidative phenotype of a pediatric population in Tlaltizapan, Morelos, using dextromethorphan as a metabolic probe. Materials and methods: This prospective, transversal, descriptive and experimental study was performed in a Mexican Rural Research Centre, located in Tlaltizapan, Morelos, a dependence of the National Institute of Pediatrics. It includes the phenotyping of a healthy pediatric population by evaluating their urinary excretion of dextromethorphan and its metabolites. Results: Five children (29%) of the 17-subject population evaluated, were slow metabolizers, while the remaining 12 children (71%) were non-slow or fast metabolizers. Conclusion: Clinically the type of metabolism within a population, whether slow or fast, indicates that individuals in both extremes of the histogram are in high risk of having adverse reactions to drugs, or poor developing or failed therapeutic response receiving when CYP2D6-metabolized drugs. [ABSTRACT FROM AUTHOR]

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Background: The lack of pediatric drug formulations is a problem that has limited the prescription in that population in the long term, resulting errors in drug administration by patients. Objetive: To determine the frequency of drug consumption at a National Pediatrics Institute in a six year-period, and identify those medications for which there is no available pediatric formulation. Methods: The frequency of consumption of medications was investigated, using the data base at the Pharmacy of the National Pediatrics Institute during the period from January 2001 to June 2006. Drugs were grouped according to their frequency, identifying those not available for pediatric use which are nevertheless prescribed. Results:. About 85 different drugs were used to attend hospital demands, which were prescribed on 7514 occasions within the period of study. The most frequently used drugs were: ranitidine (4.7%), paracetamol (3.8%) and midazolam (3.7%). Our results showed that midazolam, furosemide, phenobarbital, omeprazole, prednisone and captopril were the most prescribed drugs for which there are no pediatric formulations commercially available. Conclusion: This article reports the frequency of drug consumption at a pediatric hospital and discusses it in view of the lack of adequate formulations for pediatric patients in our country. [ABSTRACT FROM AUTHOR]

Metabolic polymorphism can alter the efficiency of a treatment or influence the occurrence of adverse reactions. Cytochrome 450, includes CYP2D6 which metabolizes 20% of drugs such as antipsychotic and antidepressive. Several studies have shown significant racial differences in the prevalence of phenotypes of CYP2D6, but there is not enough information on this subject in pediatric populations. Polymorphism of cytochrome is of great importance in pediatric pharmacotherapy, because of its therapeutic limitations are due to the lack of knowledge of metabolic characterization as well as, the lack of monitoring of the treatment results. Pharmacogenetic techniques are important inasmuch as they help physicians to prescribe more adequate doses of antipsychotic drugs which are currently effective only in 30% of the patients. "Personalized medicine" is important in psychiatry in order to optimize the dose of psychoactive drugs, by means of the use of CYP2D6 phenotyping, which allows to classify patients as slow, fast, intermediate and ultrarapid metabolizers. Phenotyping is done with the use of dextromethorphan as an indicator of the metabolism of CYP2D6. After oral administration of a single 0.5 mg/kg dose of DM, its urinary concentration and that of its metabolite (dextrorphan) are measured with HPLC method for fluorescence detection. [ABSTRACT FROM AUTHOR]

Propafenone is an antiarrhythmic that has been used for the treatment of tachiarrytmias in both adults and children. The aim of this study was to analyze the pharmacologic effect of a magistral suspension of propafenone, due to lack of an adequate commercial formulation for use in children. In this study we present, a case of a 2-year-old boy that was diagnosed with Wolff-Parkinson White syndrome and treated with a magistral suspension of propafenone. He has now been one year with no symptoms, no tachycardia and no cyanosis. The clinical status of the patient under treatment with propafenone was improved through constant medical care in the Cardiological Health Care Unit. The use of a magistral formulation of propafenone developed in our laboratory offers a temporal solution due to lack of medicines for children. [ABSTRACT FROM AUTHOR]

Background: Buprenorphine (BPN) is a widely used analgesic in the pediatric population, although there are few studies on the pharmacokinetics and pharmacodynamics of this drug. Objective: The objective was to characterize the pharmacokinetics of BPN after intravenous administration and analyze the effect of age, gender, weight, height, body mass index (BMI), and drug-drug interactions as covariates. Methods: Ninety-nine children (2-10 years), who underwent orthopedic surgery under regional, general, or combined anesthesia were included. Patients evaluated according to the American Society of Anesthesiologists Physical Status Classification, who received intravenous BPN 2 μg/kg were enrolled. Blood was collected from 1-240 min. Drug plasma concentrations were determined by LC-MS/MS. Population pharmacokinetic parameters were obtained with Monolix 2021R1 software. Pearson's correlation and/or ANOVA were used for statistical analysis. Results: Age was associated with changes in clearance and central compartment volume and the female gender was associated with lower intercompartmental clearance, while BMI modified clearance, central and peripheral compartment volume. Concomitant administration of BPN with fentanyl and dexamethasone produced decreases in clearance. Conclusions: The covariates of sex, age, and BMI are directly related to the increase or decrease in BPN pharmacokinetic parameters. [ABSTRACT FROM AUTHOR]

Background: Most of bayesian pharmacokinetic studies and the influence of clinical variables have been carried out in adults., Purpose: The aim was to estimate population-based pharmacokinetic of valproic acid (VPA) and to determine the effect of treatment and additional disease on its performance in children with epilepsy., Material and Methods: For the study steady-state serum concentrations of VPA were determined from 108 epileptic patients (44 females and 64 males) who were receiving the anticonvulsant as main drug of treatment with age range since 1 to 16 years (median 4y, 6m) and weight since 5.2 to 50 kg (median 17.5 kg). All patients had their renal, hepatic and nutritional functions normal. One compartment model using interactive two-stage Bayesian approach was employed in the analysis. RESULTS; Population estimates of CL/F and V/F for VPA were 0.022 +/- 0.013 L/h and 0.217 +/- 0.134 L/kg, respectively. These estimates were significantly affected by weight, age, carbamazepine (CBZ) and gastroesophageal reflux (GER). The final regression models were: CL/F (L/h) = 0.0696 + 0.0031 (Age) + 0.0075 (Weight); and V/F (L) = 0.674 + 0.0308 (Age) + 0.0756 (Weight). Prediction of VPA serum concentration in other validation group revealed an important improvement in the predictive performance of VPA concentrations in comparison with the basic model that did not include any co-variables., Conclusions: Based on a population model of children with epilepsy, the pharmacokinetic of VPA could be altered by weight, age and the administration of CBZ and additional GER to epilepsy.

Aim: The purpose of the present study is to determine the relationship between the anticonvulsant drug use during pregnancy and the presence of malformations in the newborns., Methods: The frequency of malformations in the neonates of epileptic mothers under anticonvulsant treatment was analyzed in two periods, one from 1988 to 1992, which included 76 epileptic mothers, and another from 1996 to 2003 with 170 patients., Results: In the first period, 51 (67.1%) of mothers received monotherapy and 25 (32.9%) received polytherapy of phenytoin with carbamazepine, valproic acid or phenobarbital. In this period, 4 newborns (16%) with congenital malformations were registered. In the second period, 159 (93.5%) of the epileptic mothers received monotherapy and 11 (6.5%) received polytherapy of valproic acid with carbamazepine or phenytoin. During this period only 3 newborns 27.3% with malformations were registered., Discussion: Clinical treatment should consider the risk of using polytherapy, mainly if phenytoin or valproic acid are combined with other anticonvulsants.