Jeffrey G Stark

Worldwide Clinical Trials, King of Prussia, Pennsylvania, United States

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Publications (14)23.6 Total impact

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    Albert W Brzeczko, Ronald Leech, Jeffrey G Stark
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    ABSTRACT: Abstract Background: The personal and societal effects of methamphetamine abuse are well documented. The ease of accessibility to methamphetamine and the quality of the "high" it produces makes the drug highly desired by its abusers. Over time, many methamphetamine users will also become methamphetamine cooks, where pseudoephedrine in over-the-counter cold products is converted to methamphetamine through a simple, albeit extremely dangerous, process. New laws limiting access to these products have had limited success. No existing commercial pseudoephedrine products offer significant impediments to slow or limit the extraction and conversion of pseudoephedrine in clandestine methamphetamine laboratories. Objective and Methods: A new pseudoephedrine 30 mg tablet product using Impede technology (Nexafed®) to deter methamphetamine production has recently been introduced into the marketplace. Using methods designed to mimic clandestine laboratory processes, the ability of this product to disrupt extraction and conversion of pseudoephedrine to methamphetamine yet provide therapeutic effectiveness was evaluated. Results: Impede™ technology tablets limited the extraction and/or conversion of pseudoephedrine to methamphetamine when compared to a commercially marketed pseudoephedrine product (Sudafed®). Nexafed® tablets were also shown to be bioequivalent to the same control product, thus ensuring therapeutic equivalence. Conclusions: With the advent of new pseudoephedrine products in the marketplace with features to limit the extraction and conversion of pseudoephedrine to methamphetamine, new tools are now available to minimize the clandestine manufacture of the drug and potentially limit its social impact.
    The American Journal of Drug and Alcohol Abuse 09/2013; 39(5):284-90. · 1.55 Impact Factor
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    ABSTRACT: An immediate-release oxycodone hydrochloride formulation (IRO-A) indicated for moderate to severe pain was designed (by adding functional excipients) to discourage tampering associated with intranasal and intravenous abuse of prescription opioids. The primary objective of this study was to determine the dose proportionality of oxycodone in IRO-A tablets under fasted conditions. Secondary objectives were to assess food effects on the pharmacokinetics of IRO-A tablets, to compare the relative bioavailability of oxycodone in IRO-A tablets versus marketed oxycodone hydrochloride (IRO) tablets under fed conditions and to evaluate the single-dose safety profile of the IRO-A tablets in healthy volunteers pretreated with naltrexone. This open-label, single-dose, randomized, 5-way crossover study was conducted in healthy adults who received each of the following treatments, separated by a washout period of ≥7 days: IRO-A 1 × 5 mg, 2 × 5 mg, and 2 × 7.5 mg under fasted conditions, and IRO-A 2 × 7.5 mg and IRO 1 × 15 mg after a high-fat, high-calorie breakfast. Naltrexone was administered to minimize untoward pharmacologic effects of oxycodone. Dose proportionality (IRO-A), food effects (IRO-A), and relative bioavailability in a fed state (IRO-A and IRO) were assessed by using bioequivalence criteria (90% CIs between 80% and 125% for C(max) and AUC). Of the 35 adults enrolled in the study, 33 completed at least 1 dosing period. Most participants were male (54%) and white (69%), with a mean (SD) age of 32.6 (11.1) years and mean weight of 75.5 (12.3) kg. Plasma levels of oxycodone in IRO-A suggested dose-proportional pharmacokinetics; 90% CIs for dose-normalized C(max), AUC(0-last), and AUC(0-∞) fell within the 80% to 125% range. Concomitant food intake with IRO-A resulted in an ~14% reduction in oxycodone C(max) and an ~21% increase in AUC(0-last). The bioavailability of oxycodone from IRO-A tablets in the fed state was comparable with IRO tablets based on AUC parameters, although C(max) was ~16.5% lower. Reported or observed treatment-emergent adverse events were monitored throughout the study and were similar for IRO-A and IRO tablets. Nausea, headache, abdominal pain, and dizziness were the most common and are consistent with known effects of oxycodone after naltrexone blockade. Plasma levels of oxycodone in IRO-A tablets were compatible with proportional single-dose pharmacokinetics from 5 to 15 mg under fasted conditions. Administration of IRO-A with food suggested increased overall bioavailability relative to fasting conditions and a reduction in peak systemic exposure of oxycodone that is not expected to be clinically significant. When comparing IRO-A tablets with IRO tablets in the fed state, the overall systemic exposure of oxycodone was comparable, and peak systemic exposure was lower.
    Clinical Therapeutics 06/2012; 34(7):1601-12. · 2.59 Impact Factor
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    ABSTRACT: Snorting and intravenous use are common routes of administration for advanced opioid abusers. A tablet form of immediate-release oxycodone (IRO) developed using Aversion Technology combines immediate release (IR) oxycodone HCl with inactive functional excipients that are intended to discourage tampering associated with intranasal and intravenous abuse (IRO-A; Oxecta, Pfizer). The purpose of this single-dose, open-label, randomized, 3-period, 3-treatment crossover study was to evaluate the bioequivalence of IRO-A to the marketed immediate-release oxycodone HCl (IRO; Roxicodone, Xanodyne Pharmaceuticals Inc., Newport, KY). IRO-A was also compared with IRO-A with niacin, a product previously developed containing the same functional excipients plus niacin as an aversive agent to discourage oral overconsumption. Healthy adults (N = 40) aged 18-55 years received single 15-mg doses of IRO-A, IRO-A with niacin (60 mg), or IRO after fasting overnight. Naltrexone was administered to diminish opioid effects. Doses were separated by a ≥7-day washout. Plasma samples taken at designated time points were analyzed using liquid chromatography with tandem mass spectrometry. Geometric mean ratios for ln-transformed parameters for IRO-A and IRO were 92%, 104%, and 104% for Cmax, AUClast (AUC is area under the concentration-time curve), and AUCinf; 90% confidence intervals were within the accepted 80%-125% range. IRO-A was also bioequivalent to IRO-A with niacin. Adverse events were mild to moderate in intensity and typical of opioid therapy (nausea, headache, vomiting). Flushing only occurred when the subjects received the IRO-A with niacin treatment (9/37 subjects). The results demonstrated that IRO-A is bioequivalent to IRO and IRO-A with niacin. With features designed to discourage tampering associated with common forms of abuse, IRO-A may provide an alternative to conventional immediate-release oxycodone formulations.
    American journal of therapeutics 02/2012; · 1.29 Impact Factor
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    ABSTRACT: Fentanyl buccal soluble film (FBSF) is a small, bilayered, water-soluble polymer film (BioErodible MucoAdhesive; BEMA™) that adheres to the buccal mucosa and rapidly delivers fentanyl into the systemic circulation. It is approved for the treatment of cancer breakthrough pain in adult opioid-tolerant patients. The objective of this study was to evaluate the dose proportionality of the pharmacokinetics of FBSF in healthy subjects across a range of doses. This was a phase I, open-label, single-dose, three-period, Latin-square crossover study in which 12 healthy subjects received single FBSF doses of 200, 600 and 1200 μg with 72 hours between doses. Oral naltrexone was administered to each subject prior to and after each study dose. Serial venous blood samples were collected for 48 hours after study drug administration. Adverse events were recorded throughout the study. Dose linearity was examined using a power model (P = a × Doseb), where P represents the dependent variable (maximum plasma drug concentration [C(max)], area under the plasma concentration-time curve [AUC] from time zero to time of the last measurable concentration [AUC(last)], or AUC from time zero to infinity [AUC(∞)]), and a and b are constants. A value of b≈1 indicated linearity. Following administration of FBSF doses of 200-1200 μg, mean C(max) values increased in a linear manner with values ranging from 0.383 ng/mL to 2.19 ng/mL, respectively. Mean AUC(last) values increased from 3.001 ng·h/mL to 19.17 ng·h/mL and mean AUC(∞) increased in a linear manner from 3.456 ng·h/mL to 20.43 ng·h/mL. All reported adverse events were considered to be mild to moderate in severity. This study demonstrates that peak fentanyl plasma concentrations and overall exposure increase in a dose-proportional manner following administration of FBSF.
    Clinical Drug Investigation 01/2012; 32(1):63-71. · 1.70 Impact Factor
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    ABSTRACT: Purpose: The BioErodible MucoAdhesive (BEMA) drug delivery system is a small, bilayered, water-soluble, polymer film that adheres to the buccal mucosa and rapidly delivers medication into the systemic circulation. The objectives of this study were to evaluate the absorption of fentanyl from FBSF under various conditions and examine adherence of FBSF to the buccal mucosa. Methods: Six healthy volunteers participated in an open-label, 5-period, Latin-square, crossover study. Transmucosal fentanyl absorption of FBSF (400 μg) was assessed following consumption of hot tea or application of a warm heating pad to the cheek before and during administration. Buccal mucosa adhesion of FBSF was assessed using a placebo film. Fentanyl absorption following transdermal application of FBSF (1200 μg) was assessed by application of the moistened film to the forearm under an occlusive dressing. Results: Consumption of hot liquid or application of an external heating pad did not meaningfully increase the speed (median Tfirst 10.2 minutes and Tmax 2 hours, for all three conditions) or extent (mean AUC0-12 3.7, 4.0, and 4.4 hrng/mL for hot liquid, heating pad, and no heat, respectively) of fentanyl absorption from the FBSF unit. Five of the 6 subjects could remove the placebo film within 2 minutes of initial buccal application; however, only 3 (60%) of these subjects could reapply the film. Removal was not possible beyond 5 minutes in any subject. Plasma fentanyl concentrations were undetectable for at least 2 hours after transdermal application.Conclusions: These results demonstrate that FBSF absorption is not meaningfully altered when subjects drink hot liquids or apply external heat during buccal administration. In addition, FBSF cannot readily be removed from or reapplied to the buccal mucosa. Transdermal absorption of fentanyl from the FBSF unit is substantially slower than transmucosal absorption.
    The journal of supportive oncology 09/2010; 8(5).
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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. · 2.59 Impact Factor
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    ABSTRACT: Purpose: FBSF consists of a small, bilayered, water-soluble polymer film (BioErodible MucoAdhesive; BEMA) that adheres to the buccal mucosa and rapidly delivers fentanyl into the systemic circulation. The objectives of these studies were: (1) to understand the differences in the PK of fentanyl from the BEMA delivery system compared with oral transmucosal fentanyl citrate (OTFC); (2) to evaluate the effect of system pH on the absorption of fentanyl from the BEMA system;(3) to determine the absolute bioavailability of fentanyl from the BEMA delivery system;(4) to determine the percentage of fentanyl dose that is absorbed through the buccal mucosa; and (5) to compare the fentanyl plasma concentration profile following multiple BEMA films with an equivalent dose administered as a single film. Methods: In an open-label, 4-period, crossover study (FEN-107), 12 healthy volunteers received single 800 g doses of three FBSF formulations (pH 6.0, 7.25, 8.5) and OTFC at 48-hour intervals. In another 4-period crossover study (FEN-114), 12 healthy volunteers received single fentanyl doses (200 g intravenously, 800 g orally, and 1 x 800 g and 4 x 200 g FBSF) 72 hours apart. Serial blood samples were collected for 48 hours after each dose. Results: The FBSF formulations provided faster absorption, higher maximum plasma concentrations, and greater systemic fentanyl exposure compared to OTFC; FBSF pH 7.25 offered the best profile with a 62% higher Cmax and 46% higher AUC0-24. Absolute bioavailability of fentanyl was 71% for both single (800 g) and multi-unit (4 x 200 g) FBSF; the two regimens were bioequivalent based on Cmax and AUC. An estimated 51% of the FBSF dose was absorbed buccally. Conclusions: Plasma fentanyl concentrations were greater and observed earlier with FBSF than with OTFC. FBSF delivers a high percentage of the fentanyl dose through the buccal mucosa, resulting in high absolute bioavailability.
    PM&R 10/2009; 1(9). · 1.66 Impact Factor
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    ABSTRACT: Purpose: The BEMA (BioErodible MucoAdhesive) drug delivery system is a small, bilayered, water-soluble polymer film designed to deliver therapeutic systemic drug concentrations reliably and conveniently. Fentanyl is the initial product in the BEMA system. The objectives of these studies were to evaluate the dose linearity, consistency and predictability of FBSF dosing.Methods: Three Phase 1 studies were conducted in healthy volunteers to assess: 1) dose linearity across a range of doses; 2) consistency of repeat-dose administration; and 3) predictability when dosing with a single-unit (1 x 800 g) or multiple-unit (4 x 200 g) regimen. Results: Mean Cmax values for FBSF doses of 200, 600, and 1200 g were 0.38, 1.16, and 2.19 ng/mL, and corresponding values for mean AUCinf were 3.46, 11.72, and 20.43 nghr/mL, respectively. Two single 600 g doses of FBSF administered 3 days apart in Periods 1 and 2 produced nearly identical mean Cmax (1.08 and 1.01 ng/mL) and AUC0-12 (6.3 and 6.2 nghr/mL). Three days later, application of three 600 g doses of FBSF at 1-hour intervals in Period 3 produced a proportional increase in peak plasma concentration and exposure compared to a single dose. Application of one 800 g dose unit compared to four 200 g dose units produced identical Cmax (1.33 ng/mL) and nearly identical AUClast (11.4 vs. 11.7 nghr/mL).Conclusions: Fentanyl plasma concentrations and exposure increase linearly across the 200-1200g FBSF dose range with highly consistent dose to dose exposure from FBSF. Fentanyl exposure following 1 x 800 g and 4 x 200 g dose units were bioequivalent, supporting the recommended titration process for FBSF. The predictability and consistency of plasma concentrations with FBSF is attributed to 1) the relationship between the fentanyl dose and the film's surface area, and 2) the mucoadhesive properties of the delivery system that eliminate patient variability.
    2009 American College of Clinical Pharmacy Annual Meeting; 10/2009
  • Kai Wu, Navin Goyal, Jeffrey G Stark, Günther Hochhaus
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    ABSTRACT: Inhaled glucocorticoids continue to be first-line therapy in asthma. To improve improving patient compliance, newer inhaled glucocorticoids have been developed for once-a-day treatment. This study was interested in identifying the optimal time of dosing using 2 surrogate markers of glucocorticoid action. A previously published study on the pharmacokinetics and pharmacodynamics (cortisol and blood lymphocyte suppression) of the inhaled glucocorticoids budesonide and fluticasone propionate was reanalyzed using a population pharmacokinetic approach. A stochastic numerical simulation using NONMEM assessed the effects of time of dosing on cortisol (side effect parameter) and blood lymphocytes (side effect and effect parameter). The effects on cortisol were more pronounced when the glucocorticoids were given in the morning, whereas the effects on lymphocytes (an effect controlled by endogenous and exogenous glucocorticoids) were maximized when dosing occurred in the late afternoon or evening. Twice-daily dosing of the same dose resulted in smaller differences between maximum and minimal effects. These were of no clinical relevance. Simulations for once-daily dosing support clinical studies that reported a higher antiasthmatic effect and lower cortisol suppression when once-daily dosing occurs in the evening.
    The Journal of Clinical Pharmacology 10/2008; 48(9):1069-80. · 2.47 Impact Factor
  • Zeitschrift für Palliativmedizin 09/2008; 9(03).
  • N. Vasisht, J. Stark, A. Finn
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    ABSTRACT: Oral transmucosal delivery of fentanyl is a rapid and proven route of administration for the management of breakthrough pain in cancer patients1,2. The BEMATM drug delivery system was designed to improve oral transmucosal dosing reliability, tolerability and patient acceptance. This bilayer polymer delivery system can control the mucosal surface application area and time in contact with the mucosa, optimizing delivery and pharmacokinetics of buccally delivered fentanyl. The linearity of plasma fentanyl concentrations across a range of doses and the absolute bioavailability of fentanyl were explored in two Phase 1 pharmacokinetic studies. Single doses of BEMATM Fentanyl (200, 600, 1200 g) were administered buccally to 12 healthy volunteers 72 hours apart in an open-label, randomized, single-dose, 3-period, crossover study. In a second randomized, single-dose, 4-period, crossover study, 12 healthy volunteers received single fentanyl doses (200 g intravenously, 800 g orally, single 800 g BEMATM Fentanyl, and four 200 g BEMATM Fentanyl) 72 hours apart. All subjects were premedicated with naltrexone and monitored for safety. Serial blood samples were collected over a 48-hour period after each dose and measured for plasma fentanyl. In the dose linearity study, mean Cmax values for the 200, 600, and 1200 g BEMATM Fentanyl doses were 0.38, 1.16, and 2.19 ng/mL, respectively. The corresponding values for mean AUCinf were 3.46, 11.72, and 20.43 ng*hr/mL, respectively. The absolute bioavailability of fentanyl was >70% for both a single and multi-unit (4x200 g) regimen, of which 51% was absorbed through the buccal mucosa. BEMATM Fentanyl demonstrates linear dose-exposure and multi-unit predictability in mean peak plasma concentrations and systemic exposure of fentanyl. The BEMATM system delivers a high percentage of the fentanyl dose through the buccal mucosa, which results in an absolute fentanyl bioavailability of >70%. 1. Farrar, JNCI 1998 2. Portenoy, ClinJPain 2006 Research supported by BioDelivery Sciences International
    Journal of Pain 05/2008; 9(4):23-23. · 4.22 Impact Factor
  • Suma M Krishnan, Jeffrey G Stark
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    ABSTRACT: To evaluate the pharmacokinetics of lisdexamfetamine dimesylate (LDX; Vyvanse) in fasting healthy adult volunteers. LDX is the first pro-drug stimulant and is indicated for the treatment of attention-deficit/hyperactivity disorder. LDX was developed with the goal of providing an extended effect that is consistent throughout the day, with a reduced potential for abuse, overdose toxicity, and drug tampering. This was an open-label, multipledose phase 1 study. LDX 70 mg/d was administered in the morning to 12 subjects for 7 days. Twenty blood samples were drawn during the study. Descriptive statistics were used for pharmacokinetic parameters. Based on C(min), steady-state d-amphetamine concentration (20.6 ng/mL) was reached by day 5, whereas LDX was undetectable, and 95% of the d-amphetamine was eliminated within 48 hours following the final dose on day 7. At steady state, d-amphetamine achieved a mean +/- standard deviation C(max) of 90.1 +/- 29.6 ng/mL, with a median T(max) of 3.0 hours. The AUC(0-inf) for d-amphetamine was 1453 +/- 645.7 ng.h/mL. Complete elimination of the pro-drug occurred approximately 6 hours following the final dose on day 7. Adverse events were mild to moderate and similar to other oral amphetamines. This study describes the steady-state pharmacokinetics of LDX, a new pro-drug stimulant. Possible study limitations include an open-label design and a small sample size.
    Current Medical Research and Opinion 02/2008; 24(1):33-40. · 2.37 Impact Factor
  • Suma M Krishnan, Michael Pennick, Jeffrey G Stark
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    ABSTRACT: Attention-deficit/hyperactivity disorder (ADHD) in children often persists into adulthood and is potentially associated with significant social and occupational impairments. It is important to understand the effects of pharmacological treatments of ADHD in adults. This study aimed to assess the absorption, metabolism and elimination of lisdexamfetamine dimesylate in normal, healthy adult subjects following a single oral dose. A secondary objective was to assess the safety and tolerability of treatment. In an open-label, single-centre study, six healthy adult volunteers aged 22-52 years received a single oral 70 mg dose of (14)C-radiolabelled lisdexamfetamine dimesylate in solution following a 10-hour fast. Blood samples drawn pre-dose and at time points up to 120 hours post-dose were used for plasma pharmacokinetic analysis of the active d-amphetamine and the intact parent compound lisdexamfetamine dimesylate. Recovery of radioactivity was determined by liquid scintillation counting of blood samples (whole blood and plasma), urine samples and faecal samples collected pre-dose and at designated time points up to 120 hours post-dose. Urine samples were also analysed for the presence of amphetamine-derived metabolites. Safety was assessed by adverse event reporting, changes in physical findings, vital sign measurements, ECG measurements, and clinical laboratory test results. For intact lisdexamfetamine dimesylate, the median time to reach maximum plasma drug concentration (t(max)) was 1.00 hour, and the mean maximum plasma drug concentration (C(max)) was 58.2 +/- 28.1 ng/mL. Intact lisdexamfetamine dimesylate exhibited modest systemic exposure (area under the drug concentration-time curve from time 0 to infinity [AUC(infinity)] 67.04 +/- 18.94 ng . h/mL), and rapid elimination (mean apparent terminal elimination half-life [t((1/2)beta)] 0.47 hours). For d-amphetamine, the median t(max) was 3.00 hours, and the mean C(max) was 80.3 +/- 11.8 ng/mL. The AUC(infinity) of d-amphetamine was 1342 +/- 216.9 ng . h/mL, and elimination occurred as a first-order process. The t((1/2)beta) of d-amphetamine was 10.39 hours. Peaks consistent with amphetamine and hippuric acid were identified in urine samples by high-performance liquid chromatography radioactive profiling. Relative to dose administered, 41.5% was recovered in urine as d-amphetamine, 24.8% as hippuric acid and 2.2% as intact lisdexamfetamine dimesylate. Less than 0.3% of the administered dose was recovered in the faeces. During the 0- to 48-hour urine samples, no unexpected adverse events or clinically significant laboratory, ECG or physical examination findings related to the study medication were observed. Following a single 70 mg oral dose, lisdexamfetamine dimesylate was quickly absorbed, extensively metabolized to d-amphetamine and its derivatives, and rapidly eliminated. Systemic exposure to d-amphetamine was approximately 20-fold higher than systemic exposure to intact lisdexamfetamine dimesylate in healthy adults. Lisdexamfetamine dimesylate, administered as a single 70 mg dose, was generally well tolerated in this study.
    Clinical Drug Investigation 02/2008; 28(12):745-55. · 1.70 Impact Factor
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    ABSTRACT: In the present pharmacokinetic/pharmacodynamic (PK/PD) evaluation, cortisol, total lymphocytes, and lymphocyte subpopulations were monitored following single oral doses of two oral formulations of 3 mg budesonide (BUD) (Dosage Forms A and B) in order to assess the differential effects that BUD may have on cortisol suppression and the modulation of blood lymphocyte subtypes. On a single occasion, five subjects received one 3 mg capsule of Dosage Form A, four received three capsules of Dosage Form A (single dose of 9 mg), and five received three capsules of Dosage Form B (single dose of 9 mg). Placebo capsules were administered to six subjects in the study. Cortisol concentrations, total lymphocyte counts, and lymphocyte subpopulation counts for the CD3, CD4, CD8, CD19, and CD56/16 were fitted to an in direct PK/PD response model that described the effects of BUD on serum cortisol concentrations as well as the combined effects of BUD and cortisol on total lymphocytes and the CD3, CD4, CD8, CD19, and CD56/16 subtypes. Data were also analyzed using noncompartmental methods. The PK/PD model fitted the data with the exception of data for CD56/16. The IC(50) value for unbound BUD acting on total lymphocytes was 0.276 ng/ml while the IC(50) values for unbound BUD acting on lymphocyte subtypes ranged from 0.150 ng/ml for CD4 to 0.364 ng/ml for CD8. The IC(50) values for the effects of BUD on serum cortisol were lower (0.079 ng/ml). The results of PK/PD modeling and noncompartmental analysis indicate that BUD has a smaller effect on the CD8 subtype and larger effects on the CD4 and CD19 subtypes, relative to the effect on total lymphocytes, and that cortisol suppression, although not a direct immunological biomarker, may be a more sensitive marker for the systemic effect of corticosteroids.
    Journal of Pharmacokinetics and Pharmacodynamics 09/2006; 33(4):441-59. · 1.46 Impact Factor

Publication Stats

92 Citations
23.60 Total Impact Points


  • 2012
    • Worldwide Clinical Trials
      King of Prussia, Pennsylvania, United States
  • 2008–2010
    • University of Texas at Austin
      Austin, Texas, United States
  • 2006
    • University of Florida
      • Department of Pharmaceutics
      Gainesville, Florida, United States