Carbamazepine is a drug with a narrow therapeutic range that requires clinical monitoring, since its toxic effects are not easily predictable, and the therapeutic level can vary. Our study aimed to monitor the serum level and determine the concentration/dose relationship of carbamazepine in people with epilepsy, analyzing its clinical implication. It is observed that 90.48% of the study volunteers present serum level values (4.3–10.4 mg/L) within the therapeutic range (4–12 mg/L); 7.14% present supratherapeutic levels (12.7–14.4 mg/L), 2.38% subtherapeutic (0.93 mg/L). The findings indicate a negative correlation (r = -0.616; r2 = 0.379; p = 0.001), between the dose (mg/day) and the dose ratio (mg/L/mg/day); and a positive correlation (r = 0.544; r2 = 0.296; p = 0.002), between the dose (mg/day)-serum concentration (mg/L). ANOVA and Tukey’s test mean difference is significant (p<0.05). It is concluded that there is a positive and significant linear correlation between daily doses and serum carbamazepine concentrations, which should be considered to individualize the dose and optimize clinical results.
Risperidone/olanzapine are antipsychotics used in Peru to control symptoms of psychosis. The objective was to review the available evidence on potential pharmacokinetic interactions mediated by CYP1A2 and CYP2D6 polymorphic genes between risperidone or olanzapine and selected drugs for the treatment of COVID-19. A bibliographic search was conducted in SciELO and PubMed/Medline. The selection criteria included all types of articles in English and Spanish languages. In this review, the CYP1A2/CYP2D6/CYP3A4 genes that encode their respective enzymes have been described. The olanzapine/risperidone association increases the risk of prolonging the QT interval; chloroquine/hydroxychloroquine decreases metabolism and increases plasma concentration of risperidone; ritonavir decreases metabolism and increases plasma levels of hydroxychloroquine and lopinavir with the risk of prolonging the QT interval of the cardiac cycle and with a tendency to progression towards Torsades de Pointes. Ritonavir increases metabolism and decreases plasma levels of olanzapine. A low incidence of adverse effect was found between risperidone/azithromycin and olanzapine with azithromycin and hydroxychloroquine. Regarding the association of genes: CYP1A2*1D increases and CYP1A2*1F decreases the plasma concentration of olanzapine. Risperidone plasma levels are increased in CYP2D6 intermediate and poor metabolizers compared with normal metabolizers. Other studies indicate no significant association between poor metabolizers of CYP1A2 and CYP2D6 with increased pharmacokinetic parameters. It is concluded that there are potential risks of prolonging the QT interval due to pharmacokinetic interactions mediated by polymorphic genes CYP1A2 and CYP2D6 between risperidone or olanzapine and the drugs selected for the treatment of COVID-19.
Acetylsalicylic acid is one of the most prescribed medications in the world. It is used for prevention of acute myocardial infarction, colorectal cancer, antipyretic, and as an analgesic. This study aimed to investigate the in vitro bioequivalence of three formulations of acetylsalicylic acid, simulating physiological conditions of the dissolution medium, and analyzing its possible implication for public health. A spectrophotometric method for the quantification of acetylsalicylic acid at 265 nm was used. The dissolution test was performed using a USP apparatus 2 (paddle) with 900 mL of medium at 37 ± 0.5 °C and 75 rpm. At pH 4.5 and 6.8, the three formulations did not meet the criteria of very fast or fast dissolution (85% in ≤ 15 or 30 min, respectively). Generic A has a similarity factor (f 2 ) of 50 at pH 4.5 and 80.7 at pH 6.8; generic C f 2 values were 31.2 at pH 4.5 and 72.4 at pH 6.8. Generic B did not meet the acceptance range of the similarity factor (50−100) at pH 4.5 and 6.8. For all products tested, the dissolution efficiency was greater than 79%, and the mean dissolution time was 5.5-15.9 min. Based on the in vitro dissolution results, Generic A is bioequivalent with the innovator, whereas generics B and C are not. However, the dissolution profiles of generics A and C are similar to the innovator at pH 6.8, which is the appropriate dissolution medium for this drug.
Precision medicine seeks to individualize the dose from the beginning of phar-macological therapy based on the characteristics of each patient, genes involved in the metabolic phenotype, ethnicity or miscegenation, with the purpose to minimize adverse effects and optimize drug efficacy. The objective was to re-view studies that describe the association of the CYP2D6 and CYP2C19 genes with the tricontinental and Latin American ancestry of Peruvians. A biblio-graphic search was carried out in PubMed/Medline and SciELO, with various descriptors in Spanish and English. The results of this review confirm that the ethnic origin of Peruvians is triconti-nental due to European (mainly Spanish), African and Asian migration, in addi-tion to Latin American migration, being 60.2% mixed, 25.8% Amerindian, 5.9% white, 3.6% African descent, 1.2% Chinese and Japanese descent, and 3.3% unspecified. Studies on CYP2C19*3, CYP2D6*2, *3 and *6 have been reported in Peruvians, and the frequency is similar to that studied in Ecuadori-ans and Colombians. The CYP2C19*3, CYP2D6*3, and CYP2D6*6 alleles found in Peruvians are common in Europeans, Africans, and Asians; while CYP2D6*4 in Africans and CYP2D6*2 related to Asians. In some studies, the ethnic/gene association has not been demonstrated; while others have shown a significant association, which is why further investigation is warranted. It is concluded that the studies on CYP2D6 and CYP2C19 genes associated with the tricontinental and Latin American ancestry of Peruvians are little, and ac-cording to what has been investigated, the CYP2C19*3, CYP2D6*2, *3, *4 and *6 alleles have more related to their ancestry.
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