The Experts below are selected from a list of 63 Experts worldwide ranked by ideXlab platform
Simon J. Tulloch - One of the best experts on this subject based on the ideXlab platform.
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Single- and multiple-dose pharmacokinetics of an oral mixed amphetamine salts extended-release formulation in adults.
CNS spectrums, 2005Co-Authors: Susan B. Clausen, Stephanie C Read, Simon J. TullochAbstract:Objectives : Assess the bioavailability of mixed amphetamine salts extended-release (MAS XR) 30-mg capsules and the dose proportionality of pharmacokinetic measures for MAS XR 20,40, and 60 mg. Methods : Study A, an open-label single-period study, and Study B, a randomized, open-label, three threeway crossover study, were conducted in healthy adults in a clinical research unit. In Study A, 20 subjects received a single MAS XR 30-mg capsule by mouth daily for 7 days. In Study B, 12 subjects received single oral doses of MAS XR 20,40, and 60 mg separated by 7-14-day washout periods. Findings : Plasma dextroamphetamine (D-amphetamine) and Levoamphetamine (L-amphetamine) concentrations were measured using a validated LC-MS/MS method. In Study A, a 3:1 ratio of D-amphetamine to L-amphetamine was observed for AUC 0-∞ and C max . T max was 4.2 and 4.3 hours for D-amphetamine to Lamphetamine, respectively. In Study B, for D- and Lamphetamine, statistically significant differences were observed for AUC 0-t , AVC 0-∞ , and C max between all doses; there was a linear relationship between pharmacokinetic variables and dose and T max was similar for each isomer (range: 4.5–5.3 hours) with all given MAS XR doses. Conclusion : The extent of exposure as assessed by mean AUC 0-24 and C max reflected the 3:1 ratio of D-amphetamine to L-amphetamine in MAS XR 30-mg capsules. The pharmacokinetic profiles of MAS XR 20, 40, and 60 mg are dose proportional for the isomers.
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Pharmacokinetics of SLI381 (ADDERALL XR), an extended-release formulation of Adderall.
Journal of the American Academy of Child & Adolescent Psychiatry, 2003Co-Authors: James J. Mcgough, Sharon B. Wigal, Laurence L. Greenhill, Simon J. Tulloch, Thomas J. Spencer, Joseph Biederman, James T. Mccracken, Kelly Posner, Jeffrey Gornbein, James M. SwansonAbstract:ABSTRACT Objective To assess the pharmacokinetic (PK) properties of a single daily dose of Adderall ® (mixed amphetamine salts) and the extended-release formulation, SLI381 (ADDERALL XR™), in pediatric attention-deficit/hyperactivity disorder (ADHD). Method Fifty-one children (aged 6–12 years) with ADHD participated in a 6-week, seven-visit, PK and pharmacodynamic study. PK sampling occurred during visit 1 and again at visit 7. At visit 1, subjects received an initial oral dose of SLI381, 20 mg. At visit 7 subjects completed 1 week of medication treatment following random assignment to once-daily orally dosed SLI381 10 mg, 20 mg, or 30 mg; Adderall 10 mg; or placebo. Results PK parameters evidenced substantial intersubject variability (coefficients of variation=28–56%). Time to maximum concentration (T max ) for SLI381 versus Adderall showed average increases of 3.0 hours for dextroamphetamine ( t = −2.35, p = .04, df = 8.6) and 3.2 hours for Levoamphetamine ( t = −2.39, p = .04, df = 9.2). The d - and l -isomer concentrations were highly correlated and approximated a 3:1 ratio. Conclusions SLI381 showed extended T max values compared with Adderall and appears suitable for once-daily dosing. Intersubject variability underscores the need for individual dose titration.
Gerhard K. E. Scriba - One of the best experts on this subject based on the ideXlab platform.
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impurity profiling of dexamphetamine sulfate by cyclodextrin modified microemulsion electrokinetic chromatography
Electrophoresis, 2010Co-Authors: Sudaporn Wongwan, Gerhard K. E. ScribaAbstract:: A CD-modified microemulsion electrokinetic chromatography method has been developed and validated for dexamphetamine sulfate which allows the simultaneous determination of charged and uncharged impurities of the drug including the levorotary (R)-enantiomer. The optimized background electrolyte consisted of 1.5% w/w SDS, 0.5% w/w ethyl acetate, 3.5% w/w 1-butanol, 2.5% w/w 2-propanol and 92% w/w 50 mM sodium phosphate buffer, pH 3.0, containing 5.5% w/w sulfated β-CD. Separations were performed in a 50.2/40 cm, 50 μm id fused silica capillary at a temperature of 20°C and an applied voltage of -14 kV. Carbamazepine was used as internal standard. The assay was validated in the range of 0.1-1.0% for the related substances and 0.1-5.0% for Levoamphetamine based on a concentration of 3 mg/mL of dexamphetamine sulfate. The LOD of all analytes ranged between 0.05 and 0.2%. In commercial samples of dexamphetamine sulfate, Levoamphetamine was found at concentrations between 3.2 and 3.8%, whereas none of the other impurities could be detected.
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ce assay for simultaneous determination of charged and neutral impurities in dexamphetamine sulfate using a dual cd system
Electrophoresis, 2010Co-Authors: Sudaporn Wongwan, Bunleu Sungthong, Gerhard K. E. ScribaAbstract:: A CE assay for the simultaneous determination of charged and uncharged potential impurities (1S,2S-(+)-norpseudoephedrine, 1R,2S-(-)-norephedrine, phenylacetone and phenylacetone oxime) of dexamphetamine sulfate including the stereoisomer Levoamphetamine was developed and validated. The optimized background electrolyte consisted of a 50 mM sodium phosphate buffer, pH 3.0, containing 80 mg/mL sulfobutylether-beta-CD and 25 mg/mL sulfated beta-CD. Separations were performed in 40.2/35 cm, 50 mum id fused-silica capillaries at a temperature of 20 degrees C and an applied voltage of -10 kV. 1R,2S-(-)-ephedrine was used as internal standard. The assay was validated in the range of 0.05-1.0% for the related substances and in the range of 0.05-5.0% for Levoamphetamine. The LOD was 0.01-0.02% depending on the analyte. The assay also allowed the separation of the E,Z-stereoisomers of phenylacetone oxime. The effect of the degree of substitution of sulfobutylether-beta-CD was investigated. In commercial samples of dexamphetamine sulfate between 3.2 and 3.7% of Levoamphetamine were found. Furthermore, phenylacetone and phenylacetone oxime could be observed at the LOD, indicating the synthetic origin of the investigated samples.
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profiling of Levoamphetamine and related substances in dexamphetamine sulfate by capillary electrophoresis
Journal of Pharmaceutical and Biomedical Analysis, 2009Co-Authors: Nino G Kokiashvili, Sudaporn Wongwan, Carina Landgraf, Kristin Michaelis, Manuela Hammitzschwiedemann, Gerhard K. E. ScribaAbstract:Abstract A capillary electrophoresis method for the simultaneous determination of the enantiomeric purity of dexamphetamine as well as the analysis of 1R,2S-(−)-norephedrine and 1S,2S-(+)-norpseudoephedrine as potential impurities has been developed and validated. Heptakis-(2,3-di-O-acetyl-6-O-sulfo)-β-cyclodextrin was chosen as chiral selector upon a screening of neutral and charged cyclodextrin derivatives. Separation of the analytes was achieved in a fused-silica capillary at 20 °C using an applied voltage of 25 kV. The optimized background electrolyte consisted of a 0.1 M sodium phosphate buffer, pH 2.5, containing 10 mg/ml of the cyclodextrin. The assay was linear in the range of 0.06–5.0% of the impurities based on a concentration of 2.0 mg/ml dexamphetamine sulfate in the sample solution. Analysis of commercial dexamphetamine sulfate samples revealed the presence of 3–4% of Levoamphetamine while norephedrine or norpseudoephedrine could not be detected, indicating that the compound was prepared by fractionated crystallization of racemic amphetamine. Comparison with polarimetric measurements indicated that dexamphetamine with an enantiomeric excess as low as 80% still passes the pharmacopeial test of specific rotation while an amount of 0.06% of Levoamphetamine can be detected by capillary electrophoresis.
John S Markowitz - One of the best experts on this subject based on the ideXlab platform.
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pharmacology of methylphenidate amphetamine enantiomers and pemoline in attention deficit hyperactivity disorder
Human Psychopharmacology-clinical and Experimental, 1997Co-Authors: Kennerly S Patrick, John S MarkowitzAbstract:Racemic methylphenidate remains the drug of choice for attention-deficit hyperactivity disorder (ADHD). Methylphenidate appears to produce psychostimulation by inhibiting the presynaptic uptake of impulse-released dopamine. The absolute bioavailability of methylphenidate in humans is quite low and variable: mean 23 per cent for the therapeutic (+)-isomer and 5 per cent for the (−)-isomer. The primary site of presystemic metabolism may be the gut and/or intestinal wall. Brain concentrations of methylphenidate average eight times that of blood. A Tmax of 1·5–2·5 h, a Cmax of 6–15 ng/ml and a T1/2 of 2–3·5 h are typical. The area under the plasma concentration–time curves for immediate-release versus sustained-release formulations are nearly identical, but the relative efficacy is unresolved. Dextroamphetamine has generally been found to compare favourably with methylphenidate in ADHD; it acts through release of newly synthesized dopamine. Levoamphetamine is present as a minor component in a combination product (Adderall®), but the rationale for inclusion of the levo isomer remains unclear. Pemoline appears to both release and block the uptake of dopamine. Though rarely exhibiting sympathomimetic side-effects, potential hepatotoxicity relegates pemoline to a second-line status. © 1997 John Wiley & Sons, Ltd.
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Pharmacology of methylphenidate, amphetamine enantiomers and pemoline in attention‐deficit hyperactivity disorder
Human Psychopharmacology: Clinical and Experimental, 1997Co-Authors: Kennerly S Patrick, John S MarkowitzAbstract:Racemic methylphenidate remains the drug of choice for attention-deficit hyperactivity disorder (ADHD). Methylphenidate appears to produce psychostimulation by inhibiting the presynaptic uptake of impulse-released dopamine. The absolute bioavailability of methylphenidate in humans is quite low and variable: mean 23 per cent for the therapeutic (+)-isomer and 5 per cent for the (−)-isomer. The primary site of presystemic metabolism may be the gut and/or intestinal wall. Brain concentrations of methylphenidate average eight times that of blood. A Tmax of 1·5–2·5 h, a Cmax of 6–15 ng/ml and a T1/2 of 2–3·5 h are typical. The area under the plasma concentration–time curves for immediate-release versus sustained-release formulations are nearly identical, but the relative efficacy is unresolved. Dextroamphetamine has generally been found to compare favourably with methylphenidate in ADHD; it acts through release of newly synthesized dopamine. Levoamphetamine is present as a minor component in a combination product (Adderall®), but the rationale for inclusion of the levo isomer remains unclear. Pemoline appears to both release and block the uptake of dopamine. Though rarely exhibiting sympathomimetic side-effects, potential hepatotoxicity relegates pemoline to a second-line status. © 1997 John Wiley & Sons, Ltd.
Brooke E Hoots - One of the best experts on this subject based on the ideXlab platform.
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drug overdose deaths involving cocaine and psychostimulants with abuse potential united states 2003 2017
Morbidity and Mortality Weekly Report, 2019Co-Authors: Mbabazi Kariisa, Lawrence Scholl, Nana Wilson, Puja Seth, Brooke E HootsAbstract:: In 2016, a total of 63,632 persons died from drug overdoses in the United States (1). Drug overdose deaths involving cocaine, psychostimulants with abuse potential (psychostimulants), or both substances combined increased 42.4% from 12,122 in 2015 to 17,258 in 2016.* Psychostimulants with abuse potential include drugs such as methamphetamine, 3,4-methylenedioxy-methamphetamine (MDMA), dextroamphetamine, Levoamphetamine, methylphenidate (Ritalin), and caffeine. From 2015 to 2016, cocaine-involved and psychostimulant-involved death rates increased 52.4% and 33.3%, respectively (1). A total of 70,237 persons died from drug overdoses in the United States in 2017; approximately two thirds of these deaths involved an opioid (2). CDC analyzed 2016-2017 changes in age-adjusted death rates involving cocaine and psychostimulants by demographic characteristics, urbanization levels, U.S. Census region, 34 states, and the District of Columbia (DC). CDC also examined trends in age-adjusted cocaine-involved and psychostimulant-involved death rates from 2003 to 2017 overall, as well as with and without co-involvement of opioids. Among all 2017 drug overdose deaths, 13,942 (19.8%) involved cocaine, and 10,333 (14.7%) involved psychostimulants. Death rates increased from 2016 to 2017 for both drug categories across demographic characteristics, urbanization levels, Census regions, and states. In 2017, opioids were involved in 72.7% and 50.4% of cocaine-involved and psychostimulant-involved overdoses, respectively, and the data suggest that increases in cocaine-involved overdose deaths from 2012 to 2017 were driven primarily by synthetic opioids. Conversely, increases in psychostimulant-involved deaths from 2010 to 2017 occurred largely independent of opioids, with increased co-involvement of synthetic opioids in recent years. Provisional data from 2018 indicate that deaths involving cocaine and psychostimulants are continuing to increase.† Increases in stimulant-involved deaths are part of a growing polysubstance landscape. Increased surveillance and evidence-based multisectoral prevention and response strategies are needed to address deaths involving cocaine and psychostimulants and opioids. Enhancing linkage to care, building state and local capacity, and public health/public safety collaborations are critical components of prevention efforts.
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Drug Overdose Deaths Involving Cocaine and Psychostimulants with Abuse Potential — United States, 2003–2017
MMWR. Morbidity and mortality weekly report, 2019Co-Authors: Mbabazi Kariisa, Lawrence Scholl, Nana Wilson, Puja Seth, Brooke E HootsAbstract:In 2016, a total of 63,632 persons died from drug overdoses in the United States (1). Drug overdose deaths involving cocaine, psychostimulants with abuse potential (psychostimulants), or both substances combined increased 42.4% from 12,122 in 2015 to 17,258 in 2016.* Psychostimulants with abuse potential include drugs such as methamphetamine, 3,4-methylenedioxy-methamphetamine (MDMA), dextroamphetamine, Levoamphetamine, methylphenidate (Ritalin), and caffeine. From 2015 to 2016, cocaine-involved and psychostimulant-involved death rates increased 52.4% and 33.3%, respectively (1). A total of 70,237 persons died from drug overdoses in the United States in 2017; approximately two thirds of these deaths involved an opioid (2). CDC analyzed 2016-2017 changes in age-adjusted death rates involving cocaine and psychostimulants by demographic characteristics, urbanization levels, U.S. Census region, 34 states, and the District of Columbia (DC). CDC also examined trends in age-adjusted cocaine-involved and psychostimulant-involved death rates from 2003 to 2017 overall, as well as with and without co-involvement of opioids. Among all 2017 drug overdose deaths, 13,942 (19.8%) involved cocaine, and 10,333 (14.7%) involved psychostimulants. Death rates increased from 2016 to 2017 for both drug categories across demographic characteristics, urbanization levels, Census regions, and states. In 2017, opioids were involved in 72.7% and 50.4% of cocaine-involved and psychostimulant-involved overdoses, respectively, and the data suggest that increases in cocaine-involved overdose deaths from 2012 to 2017 were driven primarily by synthetic opioids. Conversely, increases in psychostimulant-involved deaths from 2010 to 2017 occurred largely independent of opioids, with increased co-involvement of synthetic opioids in recent years. Provisional data from 2018 indicate that deaths involving cocaine and psychostimulants are continuing to increase.† Increases in stimulant-involved deaths are part of a growing polysubstance landscape. Increased surveillance and evidence-based multisectoral prevention and response strategies are needed to address deaths involving cocaine and psychostimulants and opioids. Enhancing linkage to care, building state and local capacity, and public health/public safety collaborations are critical components of prevention efforts.
Thomas J. Spencer - One of the best experts on this subject based on the ideXlab platform.
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Pharmacokinetics of SLI381 (ADDERALL XR), an extended-release formulation of Adderall.
Journal of the American Academy of Child & Adolescent Psychiatry, 2003Co-Authors: James J. Mcgough, Sharon B. Wigal, Laurence L. Greenhill, Simon J. Tulloch, Thomas J. Spencer, Joseph Biederman, James T. Mccracken, Kelly Posner, Jeffrey Gornbein, James M. SwansonAbstract:ABSTRACT Objective To assess the pharmacokinetic (PK) properties of a single daily dose of Adderall ® (mixed amphetamine salts) and the extended-release formulation, SLI381 (ADDERALL XR™), in pediatric attention-deficit/hyperactivity disorder (ADHD). Method Fifty-one children (aged 6–12 years) with ADHD participated in a 6-week, seven-visit, PK and pharmacodynamic study. PK sampling occurred during visit 1 and again at visit 7. At visit 1, subjects received an initial oral dose of SLI381, 20 mg. At visit 7 subjects completed 1 week of medication treatment following random assignment to once-daily orally dosed SLI381 10 mg, 20 mg, or 30 mg; Adderall 10 mg; or placebo. Results PK parameters evidenced substantial intersubject variability (coefficients of variation=28–56%). Time to maximum concentration (T max ) for SLI381 versus Adderall showed average increases of 3.0 hours for dextroamphetamine ( t = −2.35, p = .04, df = 8.6) and 3.2 hours for Levoamphetamine ( t = −2.39, p = .04, df = 9.2). The d - and l -isomer concentrations were highly correlated and approximated a 3:1 ratio. Conclusions SLI381 showed extended T max values compared with Adderall and appears suitable for once-daily dosing. Intersubject variability underscores the need for individual dose titration.
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Efficacy of a Mixed Amphetamine Salts Compound in Adults With Attention-Deficit/ Hyperactivity Disorder
Archives of General Psychiatry, 2001Co-Authors: Thomas J. Spencer, Joseph Biederman, Timothy E. Wilens, Stephen V. Faraone, Jefferson B. Prince, Kristine Gerard, Robert Doyle, Asha Parekh, Jake Kagan, Sarah Kate BearmanAbstract:Background We report on a controlled trial of a mixed amphetamine salts compound (Adderall, dextroamphetamine sulfate, dextro-, Levoamphetamine sulfate, dextroamphetamine aspartate, Levoamphetamine aspartate, and dextroamphetamine saccharate) in the treatment of adult attention-deficit/hyperactivity disorder (ADHD). Methods This was a 7-week, randomized, double-blind, placebo-controlled, crossover study of Adderall in 27 well-characterized adults satisfying full DSM-IV criteria for ADHD of childhood onset and persistent symptoms into adulthood. Medication was titrated up to 30 mg twice a day. Outcome measures included the ADHD Rating Scale and the Clinical Global Impression Score. Comorbid psychiatric disorders were assessed to test for potential effects on treatment outcome. Results Treatment with Adderall at an average oral dose of 54 mg (administered in 2 daily doses) was effective and well tolerated. Drug-specific improvement in ADHD symptoms was highly significant overall (42% decrease on the ADHD Rating Scale, P P P = .001). Conclusions Adderall was effective and well tolerated in the short-term treatment of adults with ADHD. More work is needed to evaluate the long-term effects of Adderall, or other amphetamine compounds, in the treatment of adults with ADHD.