- Molecular FormulaC15H25N3O
- Average mass263.379 Da
|Applicants:||NEW RIVER PHARMACEUTICALS INC. [US/US]; The Governor Tyler, 1881 Grove Avenue, Radford, VA 24141 (US) (For All Designated States Except US).|
MICKLE, Travis [US/US]; (US) (For US Only).
KRISHNAN, Suma [US/US]; (US) (For US Only).
MONCRIEF, James, Scott [US/US]; (US) (For US Only).
LAUDERBACK, Christopher [US/US]; (US) (For US Only).
MILLER, Christal [US/US]; (US) (For US Only)
|Inventors:||MICKLE, Travis; (US).|
KRISHNAN, Suma; (US).
MONCRIEF, James, Scott; (US).
LAUDERBACK, Christopher; (US).
MILLER, Christal; (US)
Dr. Travis Mickle founded KemPharm, Inc. in late 2006. Prior to KemPharm, from January 2003 to October 2005, Dr. Mickle was Director of Drug Discovery and Chemical Development at New River Pharmaceuticals where he also served in a variety of other senior research roles since joining the firm in 2001. During his tenure at New River, Dr. Mickle was responsible for creating a strong preclinical and clinical pipeline of drugs in the areas of ADHD, pain and thyroid dysfunction. His contributions included, as principal inventor, the discovery and development of lisdexamfetamine dimesylate, the highly successful therapy for the treatment of ADHD known as Vyvanse®. In addition, Dr. Mickle was an active participant in FDA and DEA meetings representing the company’s discovery/chemistry group and was also called in as a critical scientific resource during New River’s financings and strategic partnering discussions. Before his departure, Dr. Mickle played an integral part in New River’s development into a successful publicly-traded company which was subsequently acquired for $2.6 billion by its marketing partner, Shire PLC. Dr. Mickle is also the author of more than 150 US and international patents and patent applications, as well as several research papers. Dr. Mickle holds a Ph.D in Bio-Organic Chemistry from the University of Iowa.
Senior Vice President, Regulatory Affairs
2012 - Current (over 5 years)
- Example IPreparation of N,N′-Biscarbobenzyloxy-Lisdexamfetamine (LDX-(Cbz)2)
Mechanism of action
in equal doses
|(g/mol)||(percent)||(30 mg dose)|
|25%||amphetamine aspartate monohydrate||(C9H13N)•C4H7NO4•H2O|
|amphetamine base suspension[note 11]||C9H13N|
History, society, and culture
- The ADHD-related outcome domains with the greatest proportion of significantly improved outcomes from long-term continuous stimulant therapy include academics (~55% of academic outcomes improved), driving (100% of driving outcomes improved), non-medical drug use (47% of addiction-related outcomes improved), obesity (~65% of obesity-related outcomes improved), self esteem (50% of self-esteem outcomes improved), and social function (67% of social function outcomes improved).The largest effect sizes for outcome improvements from long-term stimulant therapy occur in the domains involving academics (e.g., grade point average, achievement test scores, length of education, and education level), self-esteem (e.g., self-esteem questionnaire assessments, number of suicide attempts, and suicide rates), and social function (e.g., peer nomination scores, social skills, and quality of peer, family, and romantic relationships).Long-term combination therapy for ADHD (i.e., treatment with both a stimulant and behavioral therapy) produces even larger effect sizes for outcome improvements and improves a larger proportion of outcomes across each domain compared to long-term stimulant therapy alone.
- Cochrane Collaboration reviews are high quality meta-analytic systematic reviews of randomized controlled trials.
- The 95% confidence interval indicates that there is a 95% probability that the true number of deaths lies between 3,425 and 4,145.
- Transcription factors are proteins that increase or decrease the expression of specific genes.
- In simpler terms, this necessary and sufficient relationship means that ΔFosB overexpression in the nucleus accumbens and addiction-related behavioral and neural adaptations always occur together and never occur alone.
- NMDA receptors are voltage-dependent ligand-gated ion channels that requires simultaneous binding of glutamate and a co-agonist (d-serine or glycine) to open the ion channel.
- The review indicated that magnesium L-aspartate and magnesium chloride produce significant changes in addictive behavior; other forms of magnesium were not mentioned.
- For uniformity, molecular masses were calculated using the Lenntech Molecular Weight Calculator and were within 0.01g/mol of published pharmaceutical values.
- Amphetamine base percentage = molecular massbase / molecular masstotal. Amphetamine base percentage for Adderall = sum of component percentages / 4.
- dose = (1 / amphetamine base percentage) × scaling factor = (molecular masstotal / molecular massbase) × scaling factor. The values in this column were scaled to a 30 mg dose of dextroamphetamine sulfate. Due to pharmacological differences between these medications (e.g., differences in the release, absorption, conversion, concentration, differing effects of enantiomers, half-life, etc.), the listed values should not be considered equipotent doses.
- This product (Dyanavel XR) is an oral suspension (i.e., a drug that is suspended in a liquid and taken by mouth) that contains 2.5 mg/mL of amphetamine base. The amphetamine base contains dextro- to levo-amphetamine in a ratio of 3.2:1, which is approximately the ratio in Adderall. The product uses an ion exchange resin to achieve extended release of the amphetamine base.
|Cited Patent||Filing date||Publication date||Applicant||Title|
|US20050038121 *||Jun 1, 2004||Feb 17, 2005||New River Pharmaceuticals Inc.||Abuse resistant lysine amphetamine compounds|
|US20110196173 *||Oct 9, 2008||Aug 11, 2011||Andreas Meudt||Process for the Synthesis of Amphetamine Derivatives|
|DE1493824A1 *||Nov 23, 1964||May 22, 1969||Hoffmann La Roche||Verfahren zur Herstellung von Aminocarbonsaeureamiden|
|1||*||"Benzyl Chloroformate" in Handbook of Reagents for Organic Synthesis - Activating Agents and Protecting Groups ; Pearson et al., eds., 1999 John Wiley & Sons, pp. 46-50|
|2||*||DATABASE CAPLUS CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; Database Accession No. 1966:19805, Abstract NL 6414901, 28 July 1965|
|3||*||Smith and March. Advanced Organic Chemistry 6th ed. (501-502)|
|Citing Patent||Filing date||Publication date||Applicant||Title|
|US8614346||Jun 18, 2010||Dec 24, 2013||Cambrex Charles City, Inc.||Methods and compositions for preparation of amphetamine conjugates and salts thereof|
|WO2017003721A1||Jun 17, 2016||Jan 5, 2017||Noramco, Inc.||Process for the preparation of lisdexamfetamine and related derivatives|
- "Public Assessment Report Decentralised Procedure" (PDF). Shire Pharmaceuticals Contracts Limited. p. 14. Retrieved 23 August 2014.
- Millichap JG (2010). "Chapter 9: Medications for ADHD". In Millichap JG. Attention Deficit Hyperactivity Disorder Handbook: A Physician's Guide to ADHD (2nd ed.). New York, USA: Springer. p. 112. ISBN 9781441913968.
Table 9.2 Dextroamphetamine formulations of stimulant medication
Dexedrine [Peak:2–3 h] [Duration:5–6 h] ...
Adderall [Peak:2–3 h] [Duration:5–7 h]
Dexedrine spansules [Peak:7–8 h] [Duration:12 h] ...
Adderall XR [Peak:7–8 h] [Duration:12 h]
Vyvanse [Peak:3–4 h] [Duration:12 h]
- Brams M, Mao AR, Doyle RL (September 2008). "Onset of efficacy of long-acting psychostimulants in pediatric attention-deficit/hyperactivity disorder". Postgrad. Med. 120 (3): 69–88. PMID 18824827. doi:10.3810/pgm.2008.09.1909.
Onset of efficacy was earliest for d-MPH-ER at 0.5 hours, followed by d, l-MPH-LA at 1 to 2 hours, MCD at 1.5 hours, d, l-MPH-OR at 1 to 2 hours, MAS-XR at 1.5 to 2 hours, MTS at 2 hours, and LDX at approximately 2 hours. ... MAS-XR, and LDX have a long duration of action at 12 hours postdose
- "Vyvanse Prescribing Information" (PDF). United States Food and Drug Administration. Shire US Inc. January 2015. Retrieved 24 February 2015.
- Heal DJ, Smith SL, Gosden J, Nutt DJ (June 2013). "Amphetamine, past and present – a pharmacological and clinical perspective". J. Psychopharmacol. 27 (6): 479–496. PMC . PMID 23539642. doi:10.1177/0269881113482532.
- "Lisdexamfetamine dimesylate (generic)." Brown University Psychopharmacology Update 19.7 (2008): 1–2. Academic Search Premier. EBSCO. Web. 12 September 2010.
- "DEA – Department of Justice" (PDF). DEA – Department of Justice. Retrieved 1 July 2014.
- "DEA Office of Diversion Control" (PDF). DEA. Retrieved 1 July 2014.
- "Phase-III clinical trials in Attention-deficit hyperactivity disorder (In children, In adolescents) in Japan (PO)". Retrieved 20 March 2016.
- Carvalho M, Carmo H, Costa VM, Capela JP, Pontes H, Remião F, Carvalho F, Bastos Mde L (August 2012). "Toxicity of amphetamines: an update". Arch. Toxicol. 86 (8): 1167–1231. PMID 22392347. doi:10.1007/s00204-012-0815-5.
|Trade names||Tyvense, Elvanse, Venvanse, Vyvanse|
|Metabolism||Hydrolysis by enzymes in red blood cells initially.|
Subsequent metabolism follows Amphetamine#Pharmacokinetics.
|Onset of action||2 hours|
|Biological half-life||≤1 hour (prodrug molecule)|
9–11 hours (dextroamphetamine)
|Duration of action||12 hours|
|Chemical and physical data|
|Molar mass||263.378 g/mol|
|3D model (Jmol)|