Although the drug-metabolizing enzyme CYP2D6 has been studied extensively in subjects of differing ethnicities, limited CYP2D6 pharmacogenetic data are available for the Amerindian population and Mestizos of Mexico. Dextromethorphan hydroxylation phenotype was studied in Tepehuano Amerindian (n = 58) and Mestizo (n = 88) subjects, and 195 individuals (85 Tepehuano Amerindians and 110 Mestizos) were genotyped by polymerase chain reaction-restriction fragment length polymorphism methods to identify the frequencies of the CYP2D6*3, *4, *6, and *10 alleles. Tepehuano Amerindian subjects lacked the poor metabolizer (PM) phenotype, whereas in Mestizos the PM phenotype frequency was 6.8%. The CYP2D6*3, *6, and *10 alleles were not found in Tepehuano Amerindians. The CYP2D6*4 allele had a low frequency (0.006) in this Amerindian group. In the Mestizo group, the CYP2D6*3, *4, and *10 alleles had frequencies of 0.009, 0.131, and 0.023, respectively. The CYP2D6*6 allele was not found in Mestizos. The genotype-phenotype association was strongly statistically significant (r(2) = .45; P = .005) in Mestizos. The Tepehuano population was found to have a low phenotypic and genotypic CYP2D6 diversity and differed from other Amerindian groups. On the other hand, the frequencies of the CYP2D6 variant alleles in Mestizos were similar to those reported for whites.
IntroductionThe usual management of moderate to severe pain is based on the use of opioids. Buprenorphine (BPN) is an opioid with an analgesic potency 50 times greater than that of morphine. It is widely used in various pain models and has demonstrated efficacy and safety in adult patients; however, there are insufficient clinical trials in pediatric populations.PurposeThe aim of this study was to perform an updated meta-analysis on the implementation of BPN in the treatment of pain in the pediatric population.MethodsA bibliographic search was carried out in different biomedical databases to identify scientific papers and clinical trials with evidence of BPN use in children and adolescents.ResultsA total of 89 articles were found, of which 66 were selected. Analysis of these items revealed additional sources, and the final review included a total of 112 publications.ConclusionFew studies were found regarding the efficacy and safety of BPN use in children. In recent years, the use of this drug in the pediatric population has become widespread, so it is imperative to perform clinical trials and pharmacological and pharmacovigilance studies, which will allow researchers to develop dosage schemes based on the evidence and minimize the risk of adverse effects.
The aim of the present study was to develop a simple, selective and reliable method to quantify acetaminophen and its toxic metabolite N-acetyl-p-benzoquinoneimine (NAPQI) for pediatric studies using 100 µL plasma samples, by reverse-phase HPLC and UV detection. The assay was performed using a C₁₈ column and an isocratic elution with water-methanol-formic acid (70:30:0.15; v/v/v) as mobile phase. Linearity of the method was assayed in the range of 1-30 µg/mL for acetaminophen and 10-200 µg/mL for NAPQI, with a correlation coefficient r = 0.999 for both compounds, and inter- and intra-day coefficients of variation of less than 13%. Several commonly co-administered drugs were analyzed for selectivity and no interference with the determinations was observed. The detection and quantification limits for acetaminophen and NAPQI were 0.1 and 1 µg/mL, and 0.1 and 10 µg/mL respectively. The present method can be used to monitor acetaminophen levels using 100 µL plasma samples, which may be helpful when very small samples need to be analyzed, as in pharmacokinetics determination or drug monitoring in plasma in children. This assay is also able to detect the NAPQI for drug monitoring in patients diagnosed with acetaminophen intoxication.
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