Adderall

For learning purposes only

Dextroamphetamine:

Complete absorption: 3 hours (plasma tmax 2 hours) [7]
Half-life (adults): 10 hours
Absorption half-life (adults): 45 minutes (25 minutes for plasma) [6]
Volume of distribution: 195 L
Calculated clearance rate: 17.1 L
Mean Absorption half-life: 19 minutes
Attentin Mean Tmax: 1.5 hours [1][2]
Average onset of action: 36.2 minutes
Average duration of action: 6.5 hours after intake
Food can delay XR Tmax by 2-hours [3]
Half-life: 7.9 hours (pH-dependent)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5594082/     (Fig. 5)
Food reduces Cmax to 83.7% [10]
(Calculated half-life from alternate study: 9.1 hours https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5572767/

Effects do not correlate with amphetamine plasma concentration, they occur during the absorption phase.
The later decrease response may be related to: depletion of catecholamine stores, replacement by a 'false neurotransmitter' metabolite of amphetamine, or alteration receptor sensitivity. [5]

Dextroamphetamine is undetectable 44 hours after ingestion. [8]

Amphetamine:

Clearance rate: 0.7 L/kg/h
Volume of distribution: 4 L/kg
Bioavailability: 75%
Adderall XR increases tmax by 3.2 hours for l-amph and 3.0 hours d-amph [4]
Calculated half-life: 3.96 hours
Tmax: 2.1 hours
Half-life: 11 hours
Calculated absorption half-life: 26 minutes
Half-life: 4-12 hours based on pH
https://www.jaacap.org/article/S0890-8567%2809%2961157-6/fulltext

https://pubchem.ncbi.nlm.nih.gov/compound/Amphetamine#section=Absorption-Distribution-and-Excretion
Food can reduce Cmax to 84.7% [10]

Adderall XR

Dextroamphetamine XR tmax: 4.2 hours
Levoamphetamine XR tmax: 4.3 hours
When taken once: Range for both isomers (range:4.5-5.3 hours)
https://pubmed.ncbi.nlm.nih.gov/16344836/
Adderall XR increases d-amph tmax by 3 hours and 3.2 hours for l-amph [4]
Food can increase Adderall XR tmax by 2 hours[3]
Median tmax for d-amph as Adderall XR is 4 hours
Median tmax for l-amph as Adderall XR is 5.5 hours
Source for above: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=35744538-1704-4ee0-954d-52710cf3456d&type=display

Misc

Amphetamines slow gastric emptying by up to 70% at 3 mg/kg
Gastric reduction rate based on dose custom formula: log2(d/0.75)*10+50
with the maximum being 70%
d = dose in mg/kg
https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1038/sj.bjp.0701937 Fig. 2

Dextroamphetamine sulfate to free-base according to Wikipedia's Adderall is 0.7338
Adderall to amphetamine free-base percentage: d-amph 47.49%, l-amph 15.08%, total 62.57%
Dextroamphetamine chemical formula = C9H13N
Dextroamphetamine sulfate chemical formula = (C9H13N)2+H2SO4
Molar mass of dextroamphetamine and sulferic acid is 135.2062 g/mol and 98.079 g/mol respectively
Dextroamphetamine sulfate to freebase conversion = 135.2062*2 / (135.2062*2+98.079) = 0.73384 = 73.4%

Amphetamine limit of detection: 0.1 ng/mL
4-hydroxyamphetamine and norephedrine limit of detection: 0.5 ng/mL [9]

Metabolites:

p-hydroxyamphetamine half-life: (4 - 10) hours
p-hydroxynorephedrine half-life: (18 - 24) hours
600 mg p-hydroxynorephedrine decreased vanillylamandelic acid by 42% (in hypertensive patients)
600 mg p-hydroxynorephedrine decreased norepinephrine by 42% (in hypertensive patients)
600 mg p-hydroxynorephedrine increased normetanephrine by 400% (in hypertensive patients)
600 mg p-hydroxynorephedrine decreased dopamine by 40% (in hypertensive patients)
https://pubmed.ncbi.nlm.nih.gov/712637/
https://pubmed.ncbi.nlm.nih.gov/4348345/

PPIs (omeprazole) decreased dextroamphetamine's median tmax by 1.25 hours (from 4 to 2.75 hours) when administered as Adderall XR.
PPIs (omeprazole) decreased levoamphetamines's median tmax by 2.5 hours (from 5.5 to 3 hours) when administered as Adderall XR.
Source for above: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=35744538-1704-4ee0-954d-52710cf3456d&type=display

Fig. 7.7

Misc.

Raises dopamine by 421% (at 1 mg/kg)
Raises dopamine by 3,000% (at 2 mg/kg)
Raises Serotonin by 165% (at 1 mg/kg)
Raises Serotonin by 200% (at 2 mg/kg)
D-amphetamine:Amphetamine ratio = 3:1 = Adderall
Serotonin decreased after long-term exposure to 8.75 mg/kg twice daily for 10 days by 40-67% https://www.jstor.org/stable/1748575
Serotonin decreased by 20% from a single 15 mg/kg dose
Striatal Dopamine decreased by 95% at doses 8.75 mg/kg for 10 days
Norepinephrine decreased by 85-94% at doses 8.75 mg/kg for 10 days
Half-life decreases/increases by 7 hours for each urinary pH unit (ascorbic acid, protein, and low-carbohydrate high-protein diets decrease urinary pH by 0.58, 0.29 (0.1 pH/6–13 g), and 0.53 respectively) [11] [12] [13] [14]

[1]: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8077785/
[2]: https://pubmed.ncbi.nlm.nih.gov/14520168/
[3]: https://pubmed.ncbi.nlm.nih.gov/27488574/
[4]: https://pubmed.ncbi.nlm.nih.gov/12921476
[5]: https://pubmed.ncbi.nlm.nih.gov/111276/
[6]: https://www.ncbi.nlm.nih.gov/books/NBK507808/
[7]: https://ntrs.nasa.gov/api/citations/19960050118/downloads/19960050118.pdf
[8]: https://diabetesjournals.org/care/article/27/12/3020/26415/ADHD-A-Diabetic-Hyperglycemic-Dilemma
[9]: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8400571/
[10]: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6544597/
[11]: https://pubmed.ncbi.nlm.nih.gov/7361797/
[12]: https://www.cambridge.org/core/journals/british-journal-of-nutrition/article/urine-ph-is-an-indicator-of-dietary-acidbase-load-fruit-and-vegetables-and-meat-intakes-results-from-the-european-prospective-investigation-into-cancer-and-nutrition-epicnorfolk-population-study/CC06EEB3716BC63A34EEB2F8DC03D125
[13]: https://pubmed.ncbi.nlm.nih.gov/7785291/
[14]: https://pubmed.ncbi.nlm.nih.gov/12148098/

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