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Aims Itraconazole is a potent inhibitor of CYP3A4 activity and is often used in combination with corticosteroids. Since the latter are partly metabolized by CYP3A4, we studied the interaction between itraconazole, prednisone and methylprednisolone in healthy male subjects. Methods The effects of 4 days administration of oral itraconazole (400 mg on the first day then 200 mg day-1 for 3 days) on the pharmacokinetics of prednisolone after a single oral dose of prednisone (60 mg) and the pharmacokinetics of methylprednisolone after single oral dose of methylprednisolone (48 mg) were studied in 14 healthy male subjects in a two-period cross-over trial. Plasma cortisol concentrations were determined as a pharmacodynamic index. Results Itraconazole increased the mean area under the methylprednisolone concentration-time curve from 2773 ng ml-1 h to 7011 ng ml-1 h (P < 0.001) and the elimination half-life from 3.2 h to 5.5 h (P < 0.001). The pharmacokinetics of prednisolone were unchanged. Cortisol concentrations at 24 h were lower after administration of methylprednisolone with itraconazole than after methylprednisolone alone (24 ng ml-1 vs 109 ng ml-1, P < 0.001). Conclusions Itraconazole increased methylprednisolone concentrations markedly with enhanced suppression of endogenous cortisol secretion, but had no effect on prednisolone pharmacokinetics. The pharmacokinetic interaction between methylprednisolone and itraconazole is probably related to inhibition of hepatic CYP3A4 activity by itraconazole. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the efficacy of nortriptyline (NOR) added to a multi-component smoking cessation intervention, which included cognitive-behavioural therapy (CBT) and provision of nicotine replacement therapy (NRT)., Design: Randomized controlled trial (RCT) comparing two study groups with blinded follow-up at 3, 6 and 12 months. Both groups received a multi-component smoking cessation intervention comprising two half-hour individual sessions of CBT and NRT with either active NOR or placebo., Setting: Prisons in New South Wales (17) and Queensland (one), Australia., Participants: A total of 425 male prisoners met inclusion criteria and were allocated to either treatment (n = 206) or control group (n = 219)., Measurements: Primary end-points at 3, 6 and 12 months were continuous abstinence, point prevalence abstinence and reporting a 50% reduction in smoking. Smoking status was confirmed by expired carbon monoxide, using a cut-point of ≤10 parts per million., Findings: Participants' demographics and baseline tobacco use were similar in treatment and control groups. Based on an intention-to-treat analysis, continuous abstinence between the treatment and control groups was not significantly different at 3 months (23.8 versus 16.4%), 6 months (17.5 versus 12.3%) and 12 months (11.7 versus 11.9%)., Conclusion: Adding nortriptyline to a smoking cessation treatment package consisting of behavioural support and nicotine replacement therapy does not appear to improve long-term abstinence rates in male prisoners., (© 2012 The Authors, Addiction © 2012 Society for the Study of Addiction.)

Tissue samples from lung cancer patients who had worked at a copper smelter and from controls were collected and classified by a panel of pathologists: 38% of the cancers were found to be adenocarcinomas, compared to 12% among the controls, a statistically significant difference (p less than 0.05). The predominance of adenocarcinomas was associated with arsenic exposure. This finding is not consistent with Kreyberg's hypothesis that small-cell undifferentiated and epidermoid carcinomas are the only type that increase in response to inhaled carcinogens [1962].