What is the recommended timing for drawing lithium levels in a 75kg female patient with bipolar disorder and multiple sclerosis, who has a history of lithium toxicity and is re-initiating sustained-release lithium (lithium carbonate) therapy?

Lithium Level Timing: 12 Hours Before Next Dose vs. 12 Hours After Evening Dose

For patients on once-daily sustained-release lithium dosing, serum lithium levels should be drawn 24 hours after the last dose (immediately before the next dose), not 12 hours after the evening dose, as the 12-hour level will be artificially elevated by approximately 1.3-fold compared to the true trough level. 1

Evidence-Based Rationale for Timing

The Critical Distinction Between Dosing Schedules

• The FDA label explicitly states that blood samples for serum lithium determination should be drawn "immediately prior to the next dose when lithium concentrations are relatively stable (i.e., 8-12 hours after the previous dose)" 2

• This FDA guidance was developed in the era when lithium was predominantly given in divided doses (twice or three times daily), making the 12-hour post-dose timing appropriate for capturing trough levels 2, 3

• With sustained-release preparations given once daily, the pharmacokinetic profile changes dramatically: peak concentrations occur at 4-5 hours (versus 1-2 hours for immediate-release), and the elimination half-life of 18-36 hours means true trough occurs at 24 hours, not 12 hours 3

Direct Evidence for Once-Daily Dosing

• A prospective study of 48 patients taking once-daily sustained-release lithium demonstrated that serum lithium levels at 12 hours post-dose were 1.3 times higher than levels at 24 hours (the true trough) 1

• The mean serum lithium level at 12 hours was 0.82 mmol/L compared to 0.60 mmol/L at 24 hours in the same patients 1

• Drawing levels at 12 hours in patients on once-daily dosing results in falsely elevated readings that may lead clinicians to maintain patients on lower than required doses of lithium 1

Pharmacokinetic Principles Supporting 24-Hour Timing

• Sustained-release lithium formulations result in 30-50% reductions in peak plasma concentrations without major changes in the area under the curve, creating a flatter concentration-time profile 3

• The therapeutic range of 0.6-0.8 mmol/L (or 0.8-1.2 mmol/L for acute treatment) is based on trough levels measured at steady-state, which for once-daily dosing occurs at 24 hours 3, 4

• Maintaining consistency in timing of blood sampling relative to dosing schedule is essential for accurate interpretation of lithium levels and dose adjustments 4

Clinical Algorithm for Lithium Level Timing

For Once-Daily Dosing (Sustained-Release Formulations)

• Draw serum lithium level at 24 hours after the last dose (immediately before the next scheduled dose) 1

• This represents the true trough level and should be used for all dose adjustments and therapeutic monitoring 1

• Target therapeutic range: 0.6-0.8 mmol/L for maintenance, 0.8-1.2 mmol/L for acute mania 2, 3

For Twice-Daily or Three-Times-Daily Dosing (Standard Formulations)

• Draw serum lithium level at 12 hours after the last dose (typically before the morning dose if dosing at 8 AM and 8 PM) 2, 3

• This timing captures the trough level for divided-dose regimens 3

• The 12-hour timing is appropriate because the dosing interval is shorter and peak-to-trough fluctuations are different 3

Common Pitfalls to Avoid

• Never apply the 12-hour rule universally without considering the dosing schedule—this is the most common error in lithium monitoring 1

• Drawing levels at 12 hours for once-daily dosing will overestimate the true trough by approximately 30%, potentially leading to underdosing and treatment failure 1

• Inconsistent timing of blood draws relative to dosing creates unreliable data that cannot be used to guide therapy 4

• Failing to specify whether the patient is on once-daily versus divided dosing when ordering lithium levels leads to misinterpretation of results 1

Special Considerations for Your Patient

• Given this patient's history of lithium toxicity and multiple sclerosis (which may affect renal function), precise therapeutic monitoring is even more critical 2

• For sustained-release lithium carbonate given once daily, the 24-hour trough level is mandatory to avoid both underdosing (risking relapse) and overdosing (risking toxicity recurrence) 1

• The therapeutic range should be individualized based on efficacy and tolerability, but the timing of the blood draw must be standardized to 24 hours post-dose for once-daily regimens 4