Predictors of pharmacological treatment outcomes with atomoxetine or methylphenidate in patients with attention-deficit/hyperactivity disorder from China, Egypt, Lebanon, Russian Federation, Taiwan, and United Arab Emirates.

BACKGROUND: The reduced availability of data from non-Western countries limits our ability to understand attention-deficit/hyperactivity disorder (ADHD) treatment outcomes, specifically, adherence and persistence of ADHD in children and adolescents. This analysis assessed predictors of treatment outcomes in a non-Western cohort of patients with ADHD treated with atomoxetine or methylphenidate. METHODS: Data from a 12-month, prospective, observational study in outpatients aged 6-17 years treated with atomoxetine (N = 234) or methylphenidate (N = 221) were analysed post hoc to determine potential predictors of treatment outcomes. Participating countries included the Russian Federation, China, Taiwan, Egypt, United Arab Emirates and Lebanon. Factors associated with remission were analysed with stepwise multiple logistic regression and classification and regression trees (CART). Cox proportional hazards models with propensity score adjustment assessed differences in atomoxetine persistence among initial-dose cohorts. RESULTS: In patients treated with atomoxetine who had available dosing information (N = 134), Cox proportional hazards revealed lower (< 0.5 mg/kg) initial dose was significantly associated with shorter medication persistence (p < 0.01). multiple logistic regression analysis revealed greater rates of remission for atomoxetine-treated patients were associated with age (older), country (United Arab Emirates) and gender (female) (all p < 0.05). CART analysis confirmed older age and lack of specific phobias were associated with greater remission rates. For methylphenidate, greater baseline weight (highly correlated with the age factor found for atomoxetine) and prior atomoxetine use were associated with greater remission rates. CONCLUSIONS: These findings may help clinicians assess factors upon initiation of ADHD treatment to improve course prediction, proper dosing and treatment adherence and persistence. TRIAL REGISTRATION: Observational study, therefore no registration.

Pharmacokinetics and metabolism of a new antitumor semisynthetic ether phospholipid, 14C-labeled plasmanyl-(N-acyl)ethanolamine, in mice bearing sarcoma Mc11.

New natural and semisynthetic antitumor ether phospholipids PNAE and PNAE(s) [plasmanyl-(N-acyl)ethanolamines] and their selective antitumor activity in vivo have been described previously. We are now presenting the pharmacokinetics, in vivo metabolism and distribution of a [14C]PNAE(s) preparation (1-O-octadecyl-2-oleoyl-sn-glycero-3-phospho-(N-[U-14C]palmitoyl) ethanolamine in the intact or Mc11-tumor-bearing BDF1 mice. Only partial degradation (about 50%-60%) of [14C]PNAE(s) was observed in vivo 24 h after i.v. administration, as detected by TLC analysis of phospholipids extracted from the blood, liver, tumor and brain of animals. Pharmacokinetic curves of [14C]PNAE(s) and its metabolites were fitted with a two-compartment model (t alpha 1/2 = 2.5 h, t beta 1/2 = 61.6 h). After repeated i.v. doses of [14C]PNAE(s) (administered on days 1, 2, 3, 4, and 5) accumulation of [14C]PNAE(s) and lyso-[14C]PNAE(s) in tumor tissue was detected. High levels of [14C]PNAE(s) were also detected in the liver, lung and spleen of animals. After i.v. administration of [14C]PNAE(s) the ether phospholipid was also detected in the brain tissue. The parmacokinetic data indicate that repeated parenteral doses of PNAE(s) are necessary to attain therapeutic concentrations in tumor tissue. The very high accumulation of [14C]PNAE(s) in the liver of animals after repeated i.v. doses, and the absence of toxic side-effects in vivo indicate a possible clinical therapeutic use of PNAE(s), especially in the treatment of tumor metastases in liver as well as in the prophylaxis of liver metastases after surgical removal of primary tumors.