What is the recommended oral dose of Dimercaptosuccinic acid (DMSA) for a heavy metal provocation test?

Oral DMSA Dosing for Heavy Metal Provocation Testing

The recommended oral dose of DMSA (Dimercaptosuccinic acid) for heavy metal provocation testing is 10 mg/kg as a single dose, with urine collection over the following 6-8 hours.

Dosing Protocol

DMSA is an effective chelating agent used to assess body burden of heavy metals through provocation testing. Based on the available evidence, the following protocol is recommended:

• Dose: 10 mg/kg as a single oral dose 1
• Collection period: 6-8 hours post-administration (optimal collection window)
• Peak excretion: Urinary lead concentration typically peaks at 2 hours after DMSA administration 1

Evidence for Dosing

Research has demonstrated that a 10 mg/kg dose of DMSA is effective for provocation testing, while higher doses (30 mg/kg/day) are more appropriate for therapeutic treatment of confirmed heavy metal poisoning 2. The 10 mg/kg dose provides sufficient chelation to assess metal burden without excessive side effects.

Collection Timing Considerations

• The 2-hour and 4-hour cumulative lead excretions after DMSA administration are highly correlated with the 8-hour total (r = 0.76 and 0.95, respectively) 1
• Cumulative excretion after DMSA typically plateaus at 6-8 hours 1
• For practical purposes, an 8-hour collection period is recommended to capture the majority of chelated metals

Pharmacokinetic Considerations

DMSA has several important pharmacokinetic properties relevant to provocation testing:

• Rapid but incomplete absorption after oral administration 3
• Most DMSA in plasma is protein-bound (mainly to albumin) through disulfide bonds 3
• Extensively metabolized to mixed disulfides of cysteine 3
• 10-25% of an orally administered dose is excreted in urine, with the majority within 24 hours 3
• Over 90% is excreted as DMSA-cysteine disulfide conjugates 3

Clinical Application

For optimal results in provocation testing:

1. Administer a single 10 mg/kg oral dose of DMSA
2. Collect urine for 6-8 hours following administration
3. Measure the concentration of the heavy metal(s) of interest in the collected urine
4. Compare results to established reference ranges for provoked samples

Potential Limitations and Precautions

• DMSA primarily chelates renal stores of heavy metals, which may not fully represent total body burden 3
• Transient elevation in transaminase activity occurs in up to 60% of patients 3
• Skin reactions occur in approximately 6% of treated patients 3
• DMSA increases urinary copper and zinc excretion, though usually not to a clinically significant extent 3

Alternative Collection Protocols

If an 8-hour collection is not feasible, shorter collection periods may be considered:

• 4-hour collection captures approximately 95% of the total 8-hour excretion 1
• 2-hour collection captures approximately 76% of the total 8-hour excretion 1

The single 10 mg/kg dose protocol provides the optimal balance between effective metal mobilization and patient safety for provocation testing purposes.