Association between plasma imatinib levels and response to treatment of chronic myeloid leukemia in patients from Manaus, Brazil.

INTRODUCTION: Imatinib mesylate (IM) is the drug of choice for the treatment of chronic myeloid leukemia (CML). However, despite most of the results obtained with this therapy being positive, some patients still present a suboptimal therapeutic response or still develop some type of resistance. Therefore, the aim of this study was to evaluate IM plasma levels in CML patients treated at a referral unit in Manaus and correlate them with variables that might interfere with these levels. METHODS: Data from 52 patients were obtained through a standardized questionnaire containing clinical, sociodemographic, lifestyle, and use of other medication information, as well as an estimate of therapeutic adherence. Additionally, blood collection was performed to measure the plasma concentration of the drug using the HPLC-UV technique. Molecular studies were done to identify the presence of polymorphism in the ABCG2 C421A membrane transporter. RESULTS: Most patients were male with a mean age of 52 ± 12.3 years (95% CI 49.0-55.9). There was a high variation in drug concentrations in the range from 0 to 4694 ng/mL, with a mean of 1558.59 ± 989.79 ng/mL (95% CI 1283.0-1834.1). CONCLUSION: Approximately two-thirds of patients were classified in the drug-level range considered therapeutic, and there was a correlation between plasma concentration and higher molecular response. Additionally, most individuals had the normal genotype for the ABCG2 C421A polymorphism but further studies should be performed to reveal the role of this variable in the outcome of the disease in this population.

Genetic polymorphisms of CYP2B6*6, CYP2C8*3 and CYP2D6*4 in vivax malaria patients from Brazilian Amazon

Abstract Genetic variability in the host metabolism of antimalarial drugs influenced by the polymorphisms of cytochrome P450 (CYP) could lead to significant changes in antimalarial treatment response. However, little is known about the frequency of alleles CYP2B6, CYP2C8, and CYP2D6 in an Amazonian population, especially with vivax malaria. Therefore, this study aimed to determine the frequency of CYP alleles CYP2B6*6, CYP2C8*3, and CYP2D6*4 in patients with vivax malaria. The study included 231 patients with vivax malaria treated at a health care reference in Manaus, northern Brazil. A sample of peripheral blood from each subject was collected to perform DNA extraction and genotypic analysis. Genotyping of polymorphisms was performed by allelic discrimination using Real-time polymerase chain reaction. The CYP2D6*4 allele was the most prevalent among patients who developed severe malaria. The frequencies of the CYP2B6*6 and CYP2D6*4 were not different between the severe and uncomplicated malaria. There was a significant association between heterozygous CYP2D6*4 and severe cases of malaria. The results are in agreement with other reports described in the literature for different populations. Future studies are needed to understand the clinical implications of the polymorphisms in patients with vivax malaria.

Population Pharmacokinetic Model of Piperacillin in Critically Ill Patients and Describing Interethnic Variation Using External Validation.

Objectives: This study aimed to develop a piperacillin population PK model for critically ill Brazil-ian patients and describe interethnic variation using an external validation. Methods: Plasma samples were obtained from 24 ICU patients during the fifth day of piperacillin treatment and assayed by HPLC-UV. Population pharmacokinetic modelling was conducted using Pmetrics. Empiric dose of 4 g IV 6- and 8-hourly were simulated for 50 and 100% fT > MIC and the probabil-ity of target attainment (PTA) and the fractional target attainment (FTA) determined. Results: A two-compartment model was designed to describe the pharmacokinetics of critically ill Brazillian patients. Clearance and volume of distribution were (mean ± SD) 3.33 ± 1.24 L h−1 and 10.69 ± 4.50 L, respectively. Creatinine clearance was positively correlated with piperacillin clearance and a high creatinine clearance was associated with lower values of PTA and FTA. An external vali-dation was performed using data from two different ethnic ICU populations (n = 30), resulting in acceptable bias and precision. Conclusion: The primary pharmacokinetic parameters obtained from critically ill Brazilian patients were similar to those observed in studies performed in critically ill patients of other ethnicities. Based on our results, the use of dose adjustment based on creati-nine clearance is required in Brazilian patients.

Off-label and unlicensed utilization of drugs in a Brazilian pediatric hospital / Utilización de medicamentos off-label y sin licencia en un hospital pediátrico de Brasil

Aim: To describe the off-label and unlicensed utilization patterns of drugs in a Brazilian pediatric hospital. Methods: The research consisted of a descriptive, prospective and cross-sectional study. Results: A total of 1,158 medicines were prescribed for 320 patients, accounting for 65 different drugs. Regarding the classification of drug utilization, the majority of the drugs were prescribed as in-label (57.2%), followed by off-label (36.4%) and by unlicensed (6.3%). The prevalences of unlicensed and off-label utilization of drugs in the studied population were 20.9 and 77.8%, respectively. Polypharmacy was highly associated to both off-label and unlicensed regimen (OR 12.9; 95% CI 3.07-54.2 and OR 3.68; 95% CI 2.02-6.69, respectively) whereas preschool children were less prone to unlicensed prescription (OR 0.39; 95% CI 0.19-0.79). Sex and length of hospitalization were not related to these outcomes. Conclusions: Further studies are necessary to verify the impact of this pattern on the occurrence of adverse drug events (AU)

Objetivo: Describir los patrones de utilización de medicamentos off-label y sin licencia en un hospital pediátrico de Brasil. Métodos: La investigación consistió en un estudio descriptivo, prospectivo y de corte transversal. Resultados: Un total de 1.158 medicamentos fueron prescritos para 320 pacientes, que representan 65 fármacos diferentes. En cuanto a la clasificación de la utilización de medicamentos, la mayoría de los medicamentos fueron prescritos como en la ficha técnica (57,2%), seguido off-label (36,4%) y por sin licencia (6,3%). Las prevalencias de uso sin licencia y off-label de drogas en la población estudiada fueron 20,9 y 77,8%, respectivamente. La polifarmacia fue muy asociada a ambos off-label y el régimen sin licencia (OR 12,9; IC del 95%: 3,07 a 54,2 y OR 3,68; IC del 95%: 2,02 a 6,69, respectivamente), mientras que los niños en edad preescolar fueron menos propensos a prescripción sin licencia (OR 0,39; 95% CI 0,19-,79). El sexo y la duración de la hospitalización no estaban relacionadas con estos resultados. Conclusiones: Son necesarios más estudios para verificar el impacto de este patrón en la ocurrencia de eventos adversos en los medicamentos (AU)

Determination of Cu, Fe, Mn, and Zn in the leaves and tea of Arrabidaea chica (Humb. & Bompl.) Verl.

Arrabidaea chica (Humb. & Bompl.) Verl. is an herb popularly used in the treatment of anemia in the Brazilian Amazon region, and little is known about its mineral content. Therefore, the elemental contents of Cu, Fe, Mn, and Zn were determined in the dried leaves and tea obtained by decoction and infusion of the three varieties of the medicinal plant using flame atomic absorption spectrometry after acid wet digestion of the samples. In general, the levels of the minerals are in good agreement with other studies involving medicinal plants, and the variety AC2 had the highest concentrations of all elements both in dried leaves and tea. Iron was found to be the most abundant in dried leaves (38.4-115.5 µg g(-1)), whereas manganese had the highest extraction efficiencies both in decoction (56.1-62.7%) and infusion (45.6-63.6%). Additionally, the decoction was more efficient in the extraction of almost all elements. The consumption of the decoction of variety AC2 may contribute to a small proportion to the daily requirements of Mn.

Two-step liquid-phase microextraction and high-performance liquid chromatography for the simultaneous analysis of the enantiomers of mefloquine and its main metabolite carboxymefloquine in plasma.

A method for the simultaneous analysis of the enantiomers of mefloquine (MQ) and its main metabolite carboxymefloquine (CMQ) in plasma is described for the first time. The assay involves two-step liquid-phase microextraction (LPME) and enantioselective high-performance liquid chromatography. In the first LPME step, the enantiomers of MQ were extracted from an alkalinized sample through a thin layer of di-n-hexyl ether immobilized in the pores of the hollow fiber and into 0.01 M perchloric acid as acceptor solution. In the second LPME step, the same sample was acidified to enable the extraction of CMQ using the same organic solvent and 0.05 M sodium hydroxide as acceptor phase. The analytes were resolved on a Chirobiotic T column in the polar-organic mode of elution and detected at 285 nm. The recovery rates from 1 mL of plasma were in the range 35-38%. The method presented limits of quantification of 50 ng/mL for all analytes and was linear up to 1,500 and 3,000 ng/mL for the enantiomers of MQ and CMQ, respectively. The plasmatic concentrations of (+)-(RS)-MQ were higher than those of (-)-(SR)-MQ after oral administration of the racemic drug to rats.

[Use of psychoactive drugs by health sciences undergraduate students at the Federal University in Amazonas, Brazil]. / Uso de psicotrópicos entre universitários da área da saúde da Universidade Federal do Amazonas, Brasil.

A survey was conducted with 521 undergraduate health sciences students from the Federal University in Amazonas, Manaus, Brazil. Lifetime alcohol consumption was reported by 87.7% students, as compared to 30.7% for tobacco, with the latter reported more frequently by males (39.7%). The most common illicit drugs were solvents (11.9%), marijuana (9.4%), amphetamines and anxiolytics (9.2% each), cocaine (2.1%), and hallucinogens (1.2%). The main reason for illicit drug use was curiosity. Lifetime use of anabolic steroids was reported by 2.1% of the students. Alcohol abuse in the previous 30 days was reported by 12.4% of the students. Events following drinking included: fights (4.7%), accidents (2.4%), classroom absenteeism (33.7%), and job absenteeism (11.8%). Another important finding was that 47.3% of students drove after drinking. Opinions on drug abuse and patterns agree with those from similar studies in other regions of Brazil.

Uso de psicotrópicos entre universitários da área da saúde da Universidade Federal do Amazonas, Brasil / Use of psychoactive drugs by health sciences undergraduate students at the Federal University in Amazonas, Brazil

Foi realizado um levantamento sobre uso de psicotrópicos entre estudantes da Faculdade de Ciências da Saúde da Universidade Federal do Amazonas, Manaus, Brasil, em uma amostra de 521 alunos. O "uso na vida" de álcool foi relatado por 87,7 por cento dos estudantes (IC95 por cento: 85,34-90,06) e o de tabaco por 30,7 por cento (IC 95 por cento: 27,39-34,01), sendo o último maior entre estudantes do sexo masculino (39,7 por cento; IC95 por cento: 33,33-46,01). As substâncias ilegais mais usadas foram: solventes (11,9 por cento; IC95 por cento: 9,57-14,23), maconha (9,4 por cento; IC95 por cento: 7,30-11,50), anfetamínicos e ansiolíticos (ambos com 9,2 por cento; IC95 por cento: 7,12-11,28), cocaína (2,1 por cento; IC95 por cento: 1,07- 3,13) e alucinógenos (1,2 por cento; IC95 por cento: 0,42-1,98). O principal motivo relatado para o uso de drogas ilegais foi a curiosidade. O "uso na vida" de esteróides anabolizantes foi citado por 2,1 por cento dos estudantes. O uso abusivo de álcool nos últimos 30 dias foi relatado por 12,4 por cento dos universitários. Entre os eventos ocorridos após a ingestão de bebidas alcoólicas, os estudantes citaram envolvimento em briga (4,7 por cento), acidentes (2,4 por cento), faltaà escola (33,7 por cento), falta ao trabalho (11,8 por cento) e conducão de veículos (47,3 por cento). A opinião sobre as drogas e o padrão de uso dos estudantes não diferem muito dos estudos semelhantes em outras regiões do Brasil.