What is the steady‑state urinary concentration of dextroamphetamine after a once‑daily 5 mg oral dose in an adult with normal renal function and typical urine pH (5.5–7.0)?

Steady-State Urinary Dextroamphetamine Concentration After 5 mg Daily Dosing

After a single 5 mg oral dose of dextroamphetamine, urinary concentrations at steady state typically range from 620 to 3,160 ng/mL, with peak excretion occurring between 2 to 18 hours post-dose, though only 19% of urine specimens consistently exceed 1,000 ng/mL at this low dose. 1

Expected Urinary Concentration Range

• Mean urinary amphetamine concentrations following a 5 mg dose show substantial individual variability, with peak concentrations ranging from 620 to 3,160 ng/mL across different subjects 1
• Approximately 30-44% of the administered dose is excreted unchanged in urine over 24 hours, meaning a 5 mg dose yields roughly 1.5-2.2 mg of unchanged dextroamphetamine in the total daily urine output 1, 2
• The time to peak urinary concentration is highly variable, occurring anywhere from 2 to 18 hours after administration, making timing of urine collection critical for interpretation 1

Critical Factors Affecting Urinary Concentration

Urine pH Dependency

• Urinary pH is the single most important determinant of amphetamine excretion, with acidic urine dramatically increasing renal clearance and urinary concentrations 3, 4
• At acidic urine pH (5.5-6.0), amphetamine excretion increases substantially because the ionized form cannot be reabsorbed from the renal tubules 4
• At alkaline urine pH (>7.0), urinary amphetamine concentrations decrease markedly due to enhanced tubular reabsorption of the non-ionized lipophilic form 3, 4
• The urine-to-blood concentration ratio averages 160-214:1, but this ratio is heavily influenced by urinary pH, with more acidic urine producing higher ratios 4

Urine Flow and Dilution

• Amphetamine excretion increases with increasing urine flow, meaning well-hydrated individuals will have lower concentrations per milliliter but higher total excretion 1
• Normalizing urinary amphetamine concentration to creatinine content improves correlation with blood levels (r = 0.60 vs r = 0.53), accounting for dilution effects 4

Practical Clinical Implications

Detection Considerations

• At the standard forensic cutoff of 1,000 ng/mL, only 19% of urine specimens test positive after a single 5 mg dose, demonstrating that this therapeutic dose frequently falls below detection thresholds 1
• Detection windows extend 67-78 hours after a single dose in most individuals, though this varies considerably with urinary pH 5
• For reliable detection of 5 mg therapeutic doses, analytical cutoffs must be lowered to 50 ng/mL or less, as used in adherence monitoring rather than forensic testing 5

Steady-State Predictions

• With once-daily dosing of 5 mg, steady-state urinary concentrations will reflect the cumulative effect of overlapping elimination phases, though amphetamine's relatively short half-life (9-11 hours) means minimal accumulation occurs 1, 2
• Expect steady-state trough urinary concentrations (pre-dose) to be substantially lower than peak concentrations, likely in the 200-800 ng/mL range for individuals with normal urine pH (6.0-7.0) 1
• Peak steady-state urinary concentrations (2-8 hours post-dose) will approximate the single-dose peak range of 620-3,160 ng/mL, assuming consistent urinary pH and hydration 1

Common Pitfalls to Avoid

• Do not interpret urinary amphetamine concentrations without knowing urinary pH, as a 10-fold difference in concentration can occur between acidic and alkaline urine from the same dose 3, 4
• Do not assume consistent urinary concentrations throughout the day, as the time of urine collection relative to dosing dramatically affects measured levels 1
• Do not rely on spot urine concentrations to estimate dose or compliance without creatinine normalization, as hydration status causes major variability 4
• Recognize that dietary factors, medications (especially antacids, urinary alkalinizers), and renal function all significantly impact urinary amphetamine levels independent of dose 1, 3