ABSTRACT
OBJECTIVE: The aim of this study was to compare the pharmacokinetic parameters between two brands of pregabalin in healthy Chilean volunteers. METHODS: A randomized, single-dose, two-period, two-sequence, crossover study design with a 2-week washout period was conducted in healthy Chilean males. Plasma samples were collected over a 12-hour period after administration of 150 mg pregabalin in each period. A validated ultra-performance liquid chromatography with positive ionization mass spectrometric detection method was used to analyze pregabalin concentration in plasma. Pharmacokinetic parameters were determined using a noncompartmental method. Bioequivalence between the test and reference products was determined when the ratio for the 90% confidence intervals (CIs) of the difference in the means of the log-transformed area under the curve (AUC)(0-t), AUC(0-∞), and maximum concentration (C(max)) of the two products were within 0.80 and 1.25. RESULTS: The study was carried out on 22 healthy Chilean volunteers. The mean (SD) C(max), AUC(0-t) and AUC(0-∞) of the test formulation (Pregobin™) of pregabalin were 2.10 (0.56) µg/ml, 10.35 (2.00) µgxh/ml and 13.92 (2.74) µgxh/ml, respectively. The mean (SD) C(max), AUC(0-t) and AUC(0-∞) of the reference formulation (Lyrica™) of pregabalin were 2.15 (0.52) µg/ml, 10.31 (1.85) µgxh/ml and 13.78 (2.25) µgxh/ml, respectively. The parametric 90% CIs for C(max), AUC(0-t), and AUC(0-∞) were 0.97-1.13, 1.01-1.04, and 0.98-1.02, respectively. CONCLUSIONS: These results suggest that both products are bioequivalent and can be used as interchangeable options in the clinical setting.
ABSTRACT
Pharmacogenetics is the study of genetically determined variations in the response to drugs and toxic agents, and their implications on disease. Recently, the discipline has acquired great relevancy due to the development of non-invasive molecular techniques that identify genetic variants in human beings. There is also a need to explain the individual differences in susceptibility to drug actions and disease risk. Genetic variants can modify the magnitude of a pharmacologic effect, toxicity threshold, secondary effects and drug interactions. There are approximately thirty families of drug-metabolizing enzymes with genetic variants that cause functional alterations and variations in pharmacologic activity. We summarize the general knowledge about genetic variants of biotransformation enzymes, their relationship with cancer risk and the role of ethnicity. Cancer pharmacogenetics is another promising and exciting research area that will explain why people with an almost identical group of genes, have a different susceptibility to cancer, whose etiology has genetic and environmental components.
Subject(s)
Aryl Hydrocarbon Hydroxylases/genetics , Genetic Predisposition to Disease/genetics , Neoplasms/genetics , Pharmacogenetics , Polymorphism, Genetic/genetics , Xenobiotics/metabolism , Aryl Hydrocarbon Hydroxylases/metabolism , Biotransformation/genetics , Cytochrome P-450 CYP1A1/genetics , Cytochrome P-450 CYP1A1/metabolism , Cytochrome P-450 CYP2E1/genetics , Cytochrome P-450 CYP2E1/metabolism , Ethnicity/genetics , Gene Frequency/genetics , Genotype , Glutathione Transferase/genetics , Glutathione Transferase/metabolism , Humans , Neoplasms/enzymologyABSTRACT
Pharmacogenetics is the study of genetically determined variations in the response to drugs and toxic agents, and their implications on disease. Recently, the discipline has acquired great relevancy due to the development of non-invasive molecular techniques that identify genetic variants in human beings. There is also a need to explain the individual differences in susceptibility to drug actions and disease risk. Genetic variants can modify the magnitude of a pharmacologic effect, toxicity threshold, secondary effects and drug interactions. There are approximately thirty families of drug-metabolizing enzymes with genetic variants that cause functional alterations and variations in pharmacologic activity. We summarize the general knowledge about genetic variants of biotransformation enzymes, their relationship with cancer risk and the role of ethnicity. Cancer pharmacogenetics is another promising and exciting research area that will explain why people with an almost identical group of genes, have a different susceptibility to cancer, whose etiology has genetic and environmental components.
Subject(s)
Humans , Aryl Hydrocarbon Hydroxylases/genetics , Genetic Predisposition to Disease/genetics , Neoplasms/genetics , Pharmacogenetics , Polymorphism, Genetic/genetics , Xenobiotics/metabolism , Aryl Hydrocarbon Hydroxylases/metabolism , Biotransformation/genetics , /genetics , /metabolism , /genetics , /metabolism , Ethnicity/genetics , Gene Frequency/genetics , Genotype , Glutathione Transferase/genetics , Glutathione Transferase/metabolism , Neoplasms/enzymologyABSTRACT
BACKGROUND: The role of susceptibility low penetrance genes and environmental factors in the etiology of prostate cancer (PCa) is unclear, but may involve in some cases multiple alleles at multiple loci. AIM: To evaluate the association of gene-gene and gene-environment interactions with PCa. PATIENTS AND METHODS: One hundred three subjects with biopsy proven PCa were studied, using a case-only design. All were interrogated about smoking habits. Polymorphisms for Glutathione-S-transferase (GS7) and Cytochrome P4501A1 (CYP1A1), were measured in DNA extracted from peripheral lymphocytes, using a restriction fragment length polymorphism analysis. RESULTS: Our findings suggest that gene-gene interactions between GSTT1 and CYP1A1 high risk genotypes were positive modifiers and had a high predictive value for the presence of PCa, compared with non-susceptibility genotypes. The interaction between susceptibility genotypes and smoking did not modify the risk for PCa. CONCLUSIONS: Gene-gene interactions may play a role modulating the susceptibility to PCa in a proportion of affected individuals.
Subject(s)
Environment , Polymorphism, Genetic , Prostatic Neoplasms/genetics , Aged , Aged, 80 and over , Cytochrome P-450 CYP1A1/genetics , Genetic Predisposition to Disease , Genotype , Glutathione Transferase/genetics , Habits , Humans , Male , Middle Aged , Risk FactorsABSTRACT
El objetivo de este trabajo fue estudiar la asociación entre algunas dimensiones psicosociales y el manejo de la enfermedad, en jóvenes que padecen diabetes tipo I. Se analizó una muestra de 133 jóvenes diabéticos que participaron en una actividad recreacional durante el verano del 2001. Se aplicó una encuesta que permitía conocer el manejo de la enfermedad (valor de la última hemoglobina glicosilada, regularidad del control y autoevaluación del manejo) y diversas dimensiones psicosociales (participación social, valoración de la religión, relación con el colegio, estado emocional y autoestima). Se encontró una estrecha relación entre el último valor de la hemoglobina glicosilada, el tiempo transcurrido desde este último examen y la autoevaluación acerca del manejo de la enfermedad. Los jóvenes que llevaban mal su tratamiento presentaron un puntaje significativamente más alto en sintomatología ansioso-depresiva y valores más bajos para la afectividad positiva y la autoestima. Los jóvenes que habían pensado periódicamente en abandonar la escuela presentaron un valor más elevado en su último control de hemoglobina glicosilada. No se encontró asociación del manejo de la enfermedad con las otras variables psicosociales que fueron estudiadas. Se concluye que existe una relación entre los estados afectivos y el manejo de la enfermedad en jóvenes diabéticos. Es importante considerar la evaluación y manejo de los estados emocionales negativos porque puede redundar en una mayor efectividad terapéutica y en una mejor calidad de vida
