Diazepam–omeprazole inhibition interaction: an in vitro investigation using human liver microsomes

1The metabolism of diazepam to its primary metabolites 3-hydroxydiazepam (3HDZ) and nordiazepam (NDZ) was evaluated in human liver microsomes. The 3HDZ pathway was the major route of metabolism representing 90% of total metabolism with a Vmax  /Km ratio of 0.50–7.26 μl min−1 mg −1 protein

THE EFFECTIVENESS OF ANGER MANAGEMENT TRAINING ON EMOTIONAL INTELLIGENCE AND ADOLESCENT IDENTITY

Background and Aim: Anger is a perfectly normal and usually useful emotion, but it can have adverse effects on interpersonal relationships if it is not properly managed. Rapid anger and loss of control can have devastating effects; hence, the present study aimed to examine the effectiveness of anger management training in improving emotional intelligence and ego-identity in adolescents. Methods: The research design was applied in terms of purpose and semi-experimental in terms of implementation method with a pretest-posttest design and a control group. To this end, 30 members of the first-grade high school students were selected by the convenience sampling method using random assignment, and 15 students were assigned to the experimental group and 15 in the control group. The research tools included the Bar-On Emotional Quotient Inventory (EQ-i), and the Measure of Ego-identity Status by Adams and Bennion (1998). The experimental group underwent anger management training for 12 sessions per week and no intervention was performed for the control group. Data analysis was performed by multivariate analysis of covariance. Results: The results indicated that there was not any significant difference between the experimental and control groups at the post-test stage in terms of emotional intelligence (F=0.06 and P>0.80), but there was a significant difference between the experimental and control groups in terms of ego-identity (F=4.88 and P<0.03). Conclusion: The results indicated that anger management training did not have any significant effect on emotional intelligence, and also the anger management training had a significant effect on ego-identity. Therefore, it is suggested that anger management training programs should be held at schools so that students can achieve the desired identity

Pharmacokinetic profile of defibrotide in patients with renal impairment

Paola Tocchetti,1 Elena Tudone,2 Jean-Francois Marier,3 Thomas C Marbury,4 Katie Zomorodi,5 Mark Eller6 1Gentium, 2Clinical Operations, Gentium, Villa Guardia, Como, Italy; 3Reporting and Analysis Services, Pharsight, a Certara Company, Montreal, Quebec, Canada; 4Orlando Clinical Research Center, Orlando, FL, 5Early Development and Clinical Pharmacology, Jazz Pharmaceuticals, 6Early Drug Development, Jazz Pharmaceuticals, Palo Alto, CA, USA Abstract: Hepatic veno-occlusive disease, also called sinusoidal obstruction syndrome (VOD/SOS), is an unpredictable, potentially life-threatening complication of hematopoietic stem cell transplant conditioning. Severe VOD/SOS, generally associated with multiorgan dysfunction (pulmonary or renal dysfunction), may be associated with &gt;80% mortality. Defibrotide, recently approved in the US, has demonstrated efficacy treating hepatic VOD/SOS with multiorgan dysfunction. Because renal impairment is prevalent in patients with VOD/SOS, this Phase I, open-label, two-part study in adults examined the effects of hemodialysis and severe or end-stage renal disease (ESRD) on defibrotide pharmacokinetics (PK). Part 1 compared defibrotide PK during single 6.25 mg/kg doses infused with and without dialysis. Part 2 assessed defibrotide plasma PK after multiple 6.25 mg/kg doses in nondialysis-dependent subjects with severe/ESRD versus healthy matching subjects. Among six subjects enrolled in Part 1, percent ratios of least-squares mean and 90% confidence intervals (CIs) on dialysis and nondialysis days were 109.71 (CI: 97.23, 123.78) for maximum observed plasma concentration (Cmax); 108.39 (CI: 97.85, 120.07) for area under the concentration&ndash;time curve to the time of the last quantifiable plasma concentration (AUC0&ndash;t); and 109.98 (CI: 99.39, 121.70) for AUC extrapolated to infinity (AUC0&ndash;&infin;). These ranges were within 80%&ndash;125%, indicating no significant effect of dialysis on defibrotide exposure/clearance. In Part 2, defibrotide exposure parameters in six subjects with severe/ESRD after multiple doses (AUC0&ndash;t, 113 &micro;g&middot;h/mL; AUC over dosing interval, 113 &micro;g&middot;h/mL; Cmax, 53.8 &micro;g/mL) were within 5%&ndash;8% of parameters after the first dose (AUC0&ndash;t, 117 &micro;g&middot;h/mL; AUC0&ndash;&infin;, 118 &micro;g&middot;h/mL; Cmax, 54.9 &micro;g/mL), indicating no accumulation. Defibrotide peak and extent of exposures in those with severe/ESRD were ~35%&ndash;37% and 50%&ndash;60% higher, respectively, versus controls, following single and multiple doses. One adverse event (vomiting, possibly drug-related) was reported. These findings support defibrotide prescribing guidance stating no dose adjustment is necessary for hemodialysis or severe/ESRD. Keywords: dialysis, end-stage renal disease, hepatic veno-occlusive disease, sinusoidal obstruction syndrome&nbsp

Population and Noncompartmental Pharmacokinetics of Sodium Oxybate Support Weight-Based Dosing in Children and Adolescents With Narcolepsy With Cataplexy

The pharmacokinetics (PKs) of sodium oxybate (SXB) was evaluated in a subset of participants from a study of SXB treatment in children (aged 7–11&nbsp;years; n&nbsp;=&nbsp;11) and adolescents (aged 12–17&nbsp;years; n&nbsp;=&nbsp;18) with narcolepsy with cataplexy. PK evaluation was conducted over 2&nbsp;nights during the period when participants received a stable nightly SXB dose. The SXB dose on night 1 was half of night 2 and was administered in two equally divided doses: dose 1 was administered &gt;&nbsp;2&nbsp;hours after the evening meal, and dose 2 was administered ≥&nbsp;4&nbsp;hours after dose 1. Noncompartmental PK analysis demonstrated higher plasma concentrations post-dose&nbsp;2 vs. post-dose 1, higher than dose-proportional increases in area under the concentration-time curve from 0 to 4&nbsp;hours (AUC0–4h) after dose 1, indicating nonlinear clearance, and better correlation between exposure and mg/kg than exposure and gram dose. To confirm the noncompartmental findings, identify factors affecting SXB PK, and compare with prior results in adults, a population PK (PopPK) model was established combining PK data from the current study with prior data from adults (132 healthy volunteers and 13 with narcolepsy). A two-compartment PopPK model with first-order absorption and nonlinear clearance from the central compartment described the data well. PopPK identified weight as the main intrinsic factor and food as the main extrinsic factor affecting SXB PK, and predicts similar PK profiles on a mg/kg basis across ages. These results, along with previously reported efficacy and safety outcomes, support weight-based SXB dose initiation in pediatric patients