Yuxin Zhang

Publications (15)59.41 Total impact

• Article: Safety and efficacy of botulinum toxin type B for treatment of sialorrhea in Parkinson's disease: a prospective double-blind trial.

  Robert Chinnapongse, Kristen Gullo, Paul Nemeth, Yuxin Zhang, Lynn Griggs
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  ABSTRACT: Sialorrhea (drooling) is a common symptom of Parkinson's disease (PD) that can significantly impair a patient's health and quality of life. Fifty-four PD subjects with troublesome sialorrhea were enrolled using a multicenter, randomized, double-blind, sequential-dose escalation design in which subjects received a single intraglandular treatment with botulinum toxin type B (doses of 1,500 Units [0.3 mL]; 2,500 Units [0.5 ml]; or 3,500 Units [0.7 ml]) or placebo. Postinjection, subjects were followed acutely for 4 weeks and long-term for up to 20 weeks. Safety/tolerability, as assessed by adverse events, was the primary outcome measure. Efficacy, as assessed by the Drooling Frequency and Severity Scale and unstimulated salivary flow rate, was secondary. Gastrointestinal-related adverse events occurred more frequently in the active groups versus placebo group (31% vs 7%), with dry mouth being most common (15%). There were no serious adverse events attributed to botulinum toxin type B or discontinuations due to adverse events from treatment. At 4 weeks postinjection, Drooling Frequency and Severity Scale scores significantly improved versus placebo (-1.3 ± 1.3) in a dose-related manner (-2.1 ± 1.2, P = 0.0191; -3.3 ± 1.4, P < 0.0001; -3.5 ± 1.1, P < 0.0001, respectively) and unstimulated salivary flow rates significantly decreased in all active groups versus placebo (P ≤ 0.0009). Furthermore, treated subjects appeared to have more sustained improvement in sialorrhea than placebo subjects. We conclude that intraglandular injection of botulinum toxin type B was safe, tolerable, and efficacious in treating sialorrhea in PD patients. Additional studies are warranted to further confirm the drug's robust efficacy, as well as evaluate its effect with repeated dosing.
  Movement Disorders 09/2011; 27(2):219-26. · 4.51 Impact Factor
• Article: RimabotulinumtoxinB effects on pain associated with cervical dystonia: results of placebo and comparator-controlled studies.

  Mark F Lew, Robert Chinnapongse, Yuxin Zhang, Meg Corliss
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  ABSTRACT: Response rate (RR) and mean improvement (MI) in the pain subscale of the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS-PS) from two placebo-controlled studies and one comparator-controlled study were evaluated to examine the effect of rimabotulinumtoxinB (BoNT-B) on cervical dystonia (CD) pain. Subjects receiving either of two doses of BoNT-B in the AN072-301 trial had an RR of 66% and 58% compared with 23% for placebo (p < .05). Subjects receiving BoNT-B in the AN072-302 trial had an RR of 49% compared with 19% for placebo (p < .05). Subjects receiving BoNT-B in the AN072-402 comparator-controlled trial had a significantly higher RR than those treated with BoNT-A (59% vs. 36%; p < .05). Additionally, subjects treated with BoNT-B in these placebo-controlled trials had significantly larger MIs than those treated with placebo (4.3 and 3.7 vs. 0.5 for AN072-301 and 3.6 vs. 0.1 for AN072-302; p < .05). Subjects treated with BoNT-B in the comparator-controlled trial demonstrated a numerically larger MI than those treated with BoNT-A (2.6 vs. 1.8; p = .1651). These results support the consideration of BoNT-B as an effective first-line botulinum toxin treatment for patients with CD who list pain as a primary complaint.
  The International journal of neuroscience 04/2010; 120(4):298-300. · 0.86 Impact Factor
• Article: A randomized, placebo-controlled, single and multiple dose study of intravenous thymosin beta4 in healthy volunteers.

  Dennis Ruff, David Crockford, Gino Girardi, Yuxin Zhang
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  ABSTRACT: Synthetic thymosin beta 4 (Tbeta4) may have a potential use in promoting myocardial cell survival during acute myocardial infarction. Four cohorts, with 10 healthy subjects each, were given a single intravenous dose of placebo or synthetic Tbeta4. Cohorts received ascending doses of either 42, 140, 420, or 1260 mg. Following safety review, subjects were given the same dose regimen daily for 14 days. Safety evaluations, incidence of Treatment-Emergent Adverse Events, and pharmacokinetic parameters were evaluated. Adverse events were infrequent, and mild or moderate in intensity. There were no dose limiting toxicities or serious adverse events. Pharmacokinetic profile for single dose showed a dose proportional response, and an increasing half-life with increasing dose. Synthetic Tbeta4 given intravenously as a single dose or in multiple daily doses for 14 days over a dose range of 42-1260 mg was well tolerated with no evidence of dose limiting toxicity. Further development for use in cardiac ischemia should be considered.
  Annals of the New York Academy of Sciences 04/2010; 1194:223-9. · 3.15 Impact Factor
• Article: Pharmacokinetics of lisdexamfetamine dimesylate and its active metabolite, d-amphetamine, with increasing oral doses of lisdexamfetamine dimesylate in children with attention-deficit/hyperactivity disorder: a single-dose, randomized, open-label, crossover study.

  Samuel W Boellner, Jeffrey G Stark, Suma Krishnan, Yuxin Zhang
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  ABSTRACT: Lisdexamfetamine dimesylate (LDX) is a long-acting oral prodrug stimulant indicated for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children 6 to 12 years old and in adults. Information on the pharmacokinetic profile of LDX in children with ADHD is lacking. The aim of this study was to assess the pharmacokinetic properties of d-amphetamine delivery from LDX, and intact LDX with increasing doses of LDX administered in children with ADHD. This single-dose, randomized, open-label, 3-period crossover study was conducted in children aged 6 to 12 years with ADHD symptoms that adversely affected school performance and required a medication switch. Eligible patients had prior stimulant experience, with good tolerability. Patients were administered a single oral dose of LDX 30, 50, or 70 mg in a randomized sequence. Each study period was separated by a 6-day washout. The pharmacokinetic properties of d-amphetamine and intact LDX were calculated over 48 hours. Adverse events (AEs) were assessed using physical examination, including vital sign measurements, and ECG. The study enrolled 18 children (mean [SD] age, 9.6 [1.9] years [range, 6-12 years]; 56% boys; weight, 36.0 [7.6] kg; 44% white, 44% black). Mean (%CV) C(max) values of d-amphetamine postdose were 53.2 (18.1), 93.3 (19.5), and 134.0 (19.4) ng/mL with LDX 30, 50, and 70 mg, respectively (T(max), approximately 3.5 hours). These findings suggest that the overall AUC for d-amphetamine was dose proportional. The intact LDX AUC was 10% to 20% higher in girls than in boys, and for d-amphetamine was <10% higher. The most commonly reported AEs, of 17 total cases, with 30-, 50-, and 70-mg LDX were anorexia (4 [22%], 7 [41%], and 8 [47%], respectively), elevated blood pressure (2 [11%], 1 [6%], and 3 [18%]), and abdominal pain (2 [11%], 2 [12%], and 2 [12%]). All AEs were mild or moderate. No serious AEs were reported. One child was withdrawn from the analysis because of pharyngitis considered to be unrelated to LDX use. The findings from this study in a small, select population of children with ADHD suggest that the concentrations of d-amphetamine, the active metabolite of LDX, after single-dose administration of LDX at increasing doses appeared to be dose proportional and had low interpatient variability.
  Clinical Therapeutics 02/2010; 32(2):252-64. · 2.32 Impact Factor
• Article: Double-blind, placebo-controlled study of the efficacy and safety of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder.

  Lenard A Adler, David W Goodman, Scott H Kollins, Richard H Weisler, Suma Krishnan, Yuxin Zhang, Joseph Biederman
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  ABSTRACT: To evaluate the efficacy and safety of 30, 50, and 70 mg/day lisdexamfetamine dimesylate compared with placebo in adults with attention-deficit/hyperactivity disorder (ADHD). Following a 7- to 28-day washout, 420 adults aged 18 to 55 years with moderate to severe ADHD (DSM-IV-TR criteria) were treated with 30, 50, or 70 mg/day lisdexamfetamine or placebo, respectively, for 4 weeks (N = 119, 117, 122, and 62, respectively). The 50- and 70- mg/day groups underwent forced-dose titration. The primary efficacy measure was the clinician-determined ADHD Rating Scale (ADHD-RS) total score. The study was conducted from May 2006 to November 2006. Treatment groups were well matched at baseline, including in ADHD-RS scores. At endpoint, changes in ADHD-RS scores were significantly greater for each lisdexamfetamine dose than for placebo (placebo = -8.2, 30 mg/day lisdexamfetamine = -16.2, 50 mg/day lisdexamfetamine = -17.4, 70 mg/day lisdexamfetamine = -18.6; all p < .0001 vs. placebo), with no differences between doses. Significant differences relative to placebo were observed in each lisdexamfetamine group, beginning at week 1 and for each week throughout. The percentage of subjects who improved (Clinical Global Impressions-Improvement scale rating < or = 2) was significantly greater for each lisdexamfetamine dose than for placebo at each week and at endpoint (placebo = 29%, 30 mg/day lisdexamfetamine = 57%, 50 mg/day lisdexamfetamine = 62%, 70 mg/day lisdexamfetamine = 61%; all p < .01). Adverse events were generally mild and included dry mouth, decreased appetite, and insomnia. All 3 lisdexamfetamine doses were significantly more effective than placebo in the treatment of adults with ADHD, with improvements noted within 1 week. Lisdexamfetamine was generally well tolerated by these patients.
  The Journal of Clinical Psychiatry 11/2008; 69(9):1364-73. · 5.80 Impact Factor
• Article: Relative bioavailability of lisdexamfetamine 70-mg capsules in fasted and fed healthy adult volunteers and in solution: a single-dose, crossover pharmacokinetic study.

  Suma Krishnan, Yuxin Zhang
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  ABSTRACT: The relative bioavailability of oral lisdexamfetamine dimesylate, a prodrug of d-amphetamine, and active d-amphetamine was assessed in an open-label, single-dose, 3-treatment, 3-period, randomized, crossover study in 18 healthy adult volunteers. Following a fast of at least 10 hours, subjects were administered an intact capsule of 70 mg lisdexamfetamine, a solution containing the capsule contents, or an intact capsule with a high-fat meal. Standard meals started 4 hours following lisdexamfetamine administration. Blood samples were taken predose (0 hours) and 0.5 to 72 hours postdose, and the concentrations of d-amphetamine and lisdexamfetamine were measured. AUC and C(max) for d-amphetamine were similar when lisdexamfetamine 70 mg was administered to healthy adults in the fed or fasted state. The AUC of intact lisdexamfetamine was similar when the latter was taken without food or in solution, but C(max) was lower when lisdexamfetamine was administered with food. The t(max) of d-amphetamine and intact lisdexamfetamine was similar when taken in solution or in the fasted state but was about 1 hour longer when taken with food. Adverse events were typical for amphetamine products. These findings indicate that food does not have a significant effect on d-amphetamine or lisdexamfetamine bioavailability in healthy adults and that lisdexamfetamine was well tolerated.
  The Journal of Clinical Pharmacology 04/2008; 48(3):293-302. · 2.91 Impact Factor
• Article: Lisdexamfetamine dimesylate and mixed amphetamine salts extended-release in children with ADHD: a double-blind, placebo-controlled, crossover analog classroom study.

  Joseph Biederman, Samuel W Boellner, Ann Childress, Frank A Lopez, Suma Krishnan, Yuxin Zhang
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  ABSTRACT: Lisdexamfetamine dimesylate is a therapeutically inactive prodrug in which d-amphetamine is covalently bound to l-lysine, a naturally occurring amino acid. Pharmacologically active d-amphetamine is released from lisdexamfetamine following oral ingestion. This phase 2, randomized, double-blind, placebo- and active-controlled crossover study compared the efficacy and safety of lisdexamfetamine (LDX: 30, 50, or 70 mg) with placebo, with mixed amphetamine salts extended-release (MAS XR: 10, 20, or 30 mg) included as a reference arm of the study, in 52 children aged 6 to 12 years with attention-deficit/hyperactivity disorder (ADHD) in an analog classroom setting. The primary efficacy measure was the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Rating Scale; secondary efficacy measures included the Permanent Product Measure of Performance (PERMP) Derived Measures, and the Clinical Global Impression (CGI) Scale. LDX treatment significantly improved scores on SKAMP-deportment, SKAMP-attention, PERMP-attempted, PERMP-correct, and CGI-improvement from baseline. Adverse events were similar for both active treatments. In a laboratory classroom environment, LDX significantly improved ADHD symptoms versus placebo in school-age children with ADHD.
  Biological Psychiatry 12/2007; 62(9):970-6. · 8.28 Impact Factor
• Article: Efficacy and tolerability of lisdexamfetamine dimesylate (NRP-104) in children with attention-deficit/hyperactivity disorder: a phase III, multicenter, randomized, double-blind, forced-dose, parallel-group study.

  Joseph Biederman, Suma Krishnan, Yuxin Zhang, James J McGough, Robert L Findling
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  ABSTRACT: Lisdexamfetamme dimesylate (LDX) is a therapeutically inactive amphetamine prodrug. It was developed with the goal of providing an extended duration of effect that is consistent throughout the day, with a reduced potential for abuse, overdose toxicity, and drug tampering. Following ingestion, the pharmacologically active d-amphetamine molecule is gradually released by rate-limited hydrolysis. The aims of this study were to assess the efficacy and tolerability of LDX in school-aged children with attention-deficit/hyperactivity disorder (ADHD) treated in the community, and to characterize the duration of action of LDX compared with placebo. This Phase III, multicenter, randomized, double-blind, forced-dose, parallel-group study was conducted at 40 centers across the United States. Male and female children aged 6 to 12 years with ADHD were randomly assigned to receive LDX 30, 50, or 70 mg with forced-dose titration, or placebo, PO QD for 4 weeks. Efficacy was assessed using the ADHD Rating Scale Version IV (ADHD-RS-IV), the Conners' Parent Rating Scale (CPR'), and the Clinical Global Impression of Improvement scale. Tolerability was assessed throughout the study. Of the 290 randomized patients (201 boys, 89 girls; mean [SD] age, 9 [1.8] years), 230 completed the trial (LDX 30 mg, n=56; LDX 50 mg, n=60; LDX 70 mg, n=60; and placebo, n=54). The most common reasons for study discontinuation (n=60) were lack of efficacy (LDX 30 mg, 1%; LDX 50 mg, 0%; LDX 70 mg, 1 %; and placebo, 17%) and adverse events (AEs) (LDX 30 mg, 9%; LDX 50 mg, 5%; LDX 70 mg, 14%; and placebo, 1%). Significant improvements in ADHD-RS-IV scores were seen with all doses of LDX compared with placebo (all, P<0.001), and in CPRS scores with all LDX doses versus placebo throughout the day (all, P<0.001 for all comparisons). Efficacy was observed by the first week of treatment, and improvements were observed throughout the day up to approximately 6 PM. The most frequently reported AEs among patients receiving LDX were typical of amphetamine products: decreased appetite (39% with active treatment vs 4% with placebo), insomnia (19% vs 3%), upper abdominal pain (12% vs 6%), headache (12% vs 10%), irritability (10% vs 0%), vomiting (9% vs 4%), weight decrease (9% vs 1%), and nausea (6% vs 3%); most were mild to moderate and occurred in the first week. In this population of children with ADHD, treatment once daily with the prodrug LDX at doses of 30 to 70 mg appeared to be effective and had a tolerability profile similar to those of currently marketed extended-release stimulants.
  Clinical Therapeutics 04/2007; 29(3):450-63. · 2.32 Impact Factor
• Article: Pharmacokinetics of mixed amphetamine salts extended release in adolescents with ADHD.

  William G Kramer, Stephanie C Read, Bao-Van Tran, Yuxin Zhang, Simon J Tulloch
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  ABSTRACT: Objective: A randomized, open-label, single-dose, three-treatment, three-period, crossover, phase I study was conducted to assess the pharmacokinetics of mixed amphetamine salts extended release (MAS XR) in adolescents with attention-deficit/hyperactivity disorder (ADHD). Methods: Two cohorts of healthy adolescents 13-17 years of age with ADHD were enrolled in the study. Seventeen subjects, weighing </=75 kg (</=165 lbs), were randomized to one of three dosing sequence groups (a single oral dose of MAS XR 10, 20, or 40 mg, followed by crossover to the alternate treatments, with a 7-day washout between treatments). Six additional subjects, weighing >75 kg (>165 lbs), were randomized similarly but received larger doses of MAS XR (20, 40, and 60 mg). Blood samples were collected before and at hours 1-12 after drug administration, as well as before and at hours 14, 24, 48, and 60. Findings: Linear pharmacokinetics of dextroamphetamine (D-amphetamine) and levoamphetamine (L-amphetamine) were observed with MAS XR in both cohorts. The pharmacokinetics of D-amphetamine and L-amphetamine did not differ between male and female adolescents. A significant decrease in maximum exposure (Cmax) and increase in half-life were seen for both isomers with increasing age, but overall exposure (AUC infinity) was not affected. Cmax and AUC infinity for both isomers decreased as body weight increased. Conclusion: Exposure to MAS XR was linear and directly proportional to the dose administered in 13-17-year-old adolescents with ADHD. The time course of drug absorption and elimination did not appear to be affected by dose at 10-40 mg in subjects weighing </=75 kg, and at 20-60 mg in subjects weighing >75 kg. Gender did not affect the pharmacokinetics of MAS XR; age and body weight influenced the profile of certain pharmacokinetic variables.
  CNS spectrums 10/2005; 10(10 Suppl 15):6-13. · 2.20 Impact Factor
• Article: A laboratory school comparison of mixed amphetamine salts extended release (Adderall XR) and atomoxetine (Strattera) in school-aged children with attention deficit/hyperactivity disorder.

  Sharon B Wigal, James J McGough, James T McCracken, Joseph Biederman, Thomas J Spencer, Kelly L Posner, Tim L Wigal, Scott H Kollins, Tanya M Clark, David A Mays, Yuxin Zhang, Simon J Tulloch
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  ABSTRACT: Mixed amphetamine salts extended release (MAS XR; Adderall XR) and atomoxetine (Strattera) were compared in children 6 to 12 years old with attention deficit/hyperactivity disorder (ADHD) combined or hyperactive/impulsive type in a randomized, double-blind, multicenter, parallel-group, forced-dose-escalation laboratory school study. Primary efficacy measure was the SKAMP (Swanson, Kotkin, Agler, M-Flynn, and Pelham) behavioral rating scale. Changes in mean SKAMP deportment scores from baseline were significantly greater for MAS XR (n = 102) than for atomoxetine (n = 101) overall (-0.56 and -0.13, respectively; p < .0001) and at each week (p < .001). Adverse events were similar for both treatment groups. The extended time course of action and greater therapeutic efficacy of MAS XR suggests that it is more effective than atomoxetine in children with ADHD.
  Journal of Attention Disorders 09/2005; 9(1):275-89. · 2.45 Impact Factor
• Article: Long-term tolerability and effectiveness of once-daily mixed amphetamine salts (Adderall XR) in children with ADHD.

  James J McGough, Joseph Biederman, Sharon B Wigal, Frank A Lopez, James T McCracken, Thomas Spencer, Yuxin Zhang, Simon J Tulloch
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  ABSTRACT: To evaluate the long-term tolerability and effectiveness of extended-release mixed amphetamine salts (MAS XR; Adderall XR) in children with attention-deficit/hyperactivity disorder (ADHD). This was a 24-month, multicenter, open-label extension of TWO placebo-controlled studies of MAS XR in children with ADHD aged 6 to 12 years. Subjects (N=568) began treatment with MAS XR 10 mg once daily, with 10-mg weekly dose increases to optimal effectiveness (maximum dose, 30 mg/d). Effectiveness was assessed with analysis of quarterly Conners Global Index Scale, Parent version (CGIS-P) scores. Tolerability was assessed by monitoring adverse events (AEs), vital signs, physical examinations, and serial laboratory tests. Significant improvements (>30%, p < .001) in CGIS-P scores were maintained during long-term treatment. Treatment was well tolerated, and most AEs were mild. The most frequently reported drug-related AEs included anorexia, insomnia, and headache. The incidence of drug-related AEs increased with increasing MAS XR dose, suggesting a dose relationship. Changes in laboratory values and vital signs were modest and not clinically meaningful. In children with ADHD, once-daily 10 mg-30 mg MAS XR was well tolerated and significant behavioral improvements were consistently maintained during 24 months of treatment.
  Journal of the American Academy of Child & Adolescent Psychiatry 06/2005; 44(6):530-8. · 6.44 Impact Factor
• Article: A pharmacokinetic/pharmacodynamic study comparing a single morning dose of adderall to twice-daily dosing in children with ADHD.

  Laurence L Greenhill, James M Swanson, Ken Steinhoff, Jane Fried, Kelly Posner, Marc Lerner, Sharon Wigal, Susan B Clausen, Yuxin Zhang, Simon Tulloch
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  ABSTRACT: To determine the pharmacokinetic and pharmacodynamic properties of once-daily versus twice-daily doses of Adderall. Following a 1-week wash-out, 12 subjects with attention-deficit/hyperactivity disorder (ADHD) entered a double-blind crossover study comparing two conditions: QD (10 mg of Adderall at 7:30 a.m. and placebo at noon) or BID (10 mg of Adderall at 7:30 a.m. and at noon). At two sites, cohorts of six subjects each were assessed on two different days by a 12-hour laboratory school protocol. Plasma concentrations of d- and l-amphetamine, vital signs, teacher ratings of classroom behavior on the SKAMP, and 10-minute Math Test performance were measured repeatedly over 12 hours. An analysis of variance used center, subject-within-center, condition, and time-after-second-dose as independent variables. The pharmacokinetic profiles revealed similar morning concentrations of d- and l-amphetamine. However, concentrations were twice as high in the afternoon for BID as QD. The two conditions showed similar pharmacodynamic profiles in the morning, although improvement in math performance and behavior was maintained into the afternoon only in the BID condition (p <.05). This study suggests that twice-daily dosing of Adderall may be an effective strategy for afternoon control of attention and deportment for children with ADHD.
  Journal of the American Academy of Child & Adolescent Psychiatry 10/2003; 42(10):1234-41. · 6.44 Impact Factor
• Article: Analog classroom assessment of a once-daily mixed amphetamine formulation, SLI381 (Adderall XR), in children with ADHD.

  James T McCracken, Joseph Biederman, Laurence L Greenhill, James M Swanson, James J McGough, Thomas J Spencer, Kelly Posner, Sharon Wigal, Caroly Pataki, Yuxin Zhang, Simon Tulloch
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  ABSTRACT: This investigation was conducted primarily to assess the safety and efficacy of SLI381 (Adderall XR), developed as a once-daily treatment for children with attention-deficit/hyperactivity disorder (ADHD). Secondary objectives included examination of the time course, pharmacokinetic, and pharmacodynamic properties of SLI381. This was a randomized, double-blind, crossover study of three doses of SLI381 (10, 20, and 30 mg), placebo, and an active control (Adderall 10 mg) given once daily to 51 children with ADHD. Weekly assessments in an analog classroom setting included blind ratings of attention and deportment and a performance measure (math test) obtained every 1.5 hours over a 12-hour period. SLI381 was well tolerated. All active treatment conditions displayed significant time course effects and were superior to placebo in improving efficacy measures. Dose-dependent improvements were evident for SLI381. SLI381 20 and 30 mg and Adderall all showed rapid improvements by 1.5 hours, but only the SLI381 20- and 30-mg doses showed continued activity at 10.5 and 12 hours for classroom behavior and math test performance versus placebo. These data provide support for the benefit of this novel, once-daily amphetamine preparation in the treatment of ADHD. The longer duration of action of SLI381 has the potential to simplify psychostimulant dosing, thus reducing dose diversion and eliminating the need for in-school administration. SLI381 appears to be a useful treatment option for many children with ADHD.
  Journal of the American Academy of Child & Adolescent Psychiatry 07/2003; 42(6):673-83. · 6.44 Impact Factor
• Article: Simulation of the effect of patient nonadherence on plasma concentrations of carbamazepine from twice-daily extended-release capsules.

  William R Garnett, Angus M McLean, Yuxin Zhang, Susan Clausen, Simon J Tulloch
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  ABSTRACT: Carbamazepine (CBZ) effectively treats simple, complex, and secondarily generalized partial seizures. Computer simulations were carried out to investigate the effect of missing or delaying doses of carbamazepine extended-release capsules (CBZ-ERC) on plasma CBZ levels and the optimal dosing strategy to return plasma concentrations to therapeutic levels. A one-compartment open model with first-order absorption and elimination was generated from the results of a previous study measuring plasma concentrations following one 400-mg fasting dose of CBZ-ERC. The model was used to simulate plasma CBZ concentrations following multiple doses given every 12 h to hypothetical long-term CBZ-treated patients, with the CBZ elimination half-life set to 13.7 h to account for enzymatic autoinduction. The model was then used to simulate plasma CBZ concentrations when a dose is taken 3, 6, or 9 h late, or when two doses are taken at one time. Predicted plasma CBZ concentrations in this simulation fell from a trough of approximately 6.4 microg/ml only to 4 microg/ml after 24 h without medication, and only to 2.5 microg/ml after 36 h without medication. Predicted plasma CBZ concentrations in this simulation never rose above 9 microg/ml, indicating that taking missed doses of CBZ-ERC as soon as remembered, up to two missed doses 3 h before taking the next scheduled dose, will not lead to harmful spikes in plasma concentrations of CBZ. The simulations suggest that taking a missed dose of CBZ-ERC as soon as remembered, up to two doses at one time, may be the best strategy to return plasma CBZ concentrations to steady-state levels. Since the model used in this study is a simplified model of a highly complex situation, caution should be used when relating these results to clinical practice until trials are conducted in patients.
  Current Medical Research and Opinion 02/2003; 19(6):519-25. · 2.38 Impact Factor
• Article: SLI381 (Adderall XR), a two-component, extended-release formulation of mixed amphetamine salts: bioavailability of three test formulations and comparison of fasted, fed, and sprinkled administration.

  Simon J Tulloch, Yuxin Zhang, Angus McLean, Kathleen N Wolf
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  ABSTRACT: To assess the bioavailability of three test formulations of a single dose of extended-release Adderall 20-mg capsules compared with two doses of immediate-release Adderall 10-mg tablets, and to assess the bioequivalence of a single 30-mg dose of the chosen extended-release Adderall formulation (designated as SLI381) administered in applesauce (sprinkled) and the same dose administered as an intact capsule with or without food. Randomized, open-label, crossover study. Clinical research unit. Forty-one healthy adults. Study A had four treatment sequences: three test formulations (A, B, and C) of a single dose of extended-release Adderall 20 mg, and two 10-mg doses of Adderall given 4 hours apart. Study B had three treatment sequences: a single dose of SLI381 30 mg as an intact capsule after overnight fast, an intact capsule after a high-fat breakfast, and the contents of a capsule sprinkled in 1 tablespoon of applesauce. The 20-mg test formulation A had comparable pharmacokinetic profiles and bioequivalence in rate and extent of drug absorption to Adderall 10 mg twice/day for both d- and l-amphetamine. Formulations B and C had statistically significant differences from the reference drug in some pharmacokinetic parameters. A 30-mg dose of SLI381 showed no significant differences in rate and extent of absorption of d- and l-amphetamine for fasted or sprinkled conditions compared with the high-fat meal condition. SLI381 20 mg/day is bioequivalent to Adderall 10 mg twice/day. SLI381 30 mg administered in applesauce is bioequivalent in terms of both rate and extent of absorption to the same dose administered as an intact capsule in both fasted and fed states.
  Pharmacotherapy 12/2002; 22(11):1405-15. · 2.90 Impact Factor