Contribution of Cytochrome P450 and ABCB1 Genetic Variability on Methadone Pharmacokinetics, Dose Requirements, and Response

Although the efficacy of methadone maintenance treatment (MMT) in opioid dependence disorder has been well established, the influence of methadone pharmacokinetics in dose requirement and clinical outcome remains controversial. The aim of this study is to analyze methadone dosage in responder and nonresponder patients considering pharmacogenetic and pharmacokinetic factors that may contribute to dosage adequacy. Opioid dependence patients (meeting Diagnostic and Statistical Manual of Mental Disorders, [4th Edition] criteria) from a MMT community program were recruited. Patients were clinically assessed and blood samples were obtained to determine plasma concentrations of (R,S)-, (R) and (S)- methadone and to study allelic variants of genes encoding CYP3A5, CYP2D6, CYP2B6, CYP2C9, CYP2C19, and P-glycoprotein. Responders and nonresponders were defined by illicit opioid consumption detected in random urinalysis. The final sample consisted in 105 opioid dependent patients of Caucasian origin. Responder patients received higher doses of methadone and have been included into treatment for a longer period. No differences were found in terms of genotype frequencies between groups. Only CYP2D6 metabolizing phenotype differences were found in outcome status, methadone dose requirements, and plasma concentrations, being higher in the ultrarapid metabolizers. No other differences were found between phenotype and responder status, methadone dose requirements, neither in methadone plasma concentrations. Pharmacokinetic factors could explain some but not all differences in MMT outcome and methadone dose requirements

Effect of Brazil's conditional cash transfer programme on tuberculosis incidence.

OBJECTIVE: To evaluate the impact of the Brazilian cash transfer programme (Bolsa Família Programme, BFP) on tuberculosis (TB) incidence in Brazil from 2004 to 2012. DESIGN: We studied tuberculosis surveillance data using a combination of an ecological multiple-group and time-trend design covering 2458 Brazilian municipalities. The main independent variable was BFP coverage and the outcome was the TB incidence rate. All study variables were obtained from national databases. We used fixed-effects negative binomial models for panel data adjusted for selected covariates and a variable representing time. RESULTS: After controlling for covariates, TB incidence rates were significantly reduced in municipalities with high BFP coverage compared with those with low and intermediate coverage (in a model with a time variable incidence rate ratio = 0.96, 95%CI 0.93-0.99). CONCLUSION: This was the first evidence of a statistically significant association between the increase in cash transfer programme coverage and a reduction in TB incidence rate. Our findings provide support for social protection interventions for tackling TB worldwide