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Subtherapeutic Acetazolamide Doses as a Noninvasive Method for Assessing Medication Adherence
Aidan J Hampson1, Jennifer R Schroeder2, Kayla N Ellefsen2,3
1Division of Therapies and Medical Consequences, National Institute on Drug Abuse, Rockville, Maryland, USA.
Clinical Pharmacology and Therapeutics
|June 5, 2020
Summary
Monitoring medication adherence in clinical trials is crucial. A new method uses 15 mg acetazolamide (ACZ) as a marker, with creatinine-normalized urinary ACZ levels accurately detecting nonadherence and confirming consumption.
Area of Science:
- Pharmacology
- Clinical Trials
- Biomarkers
Background:
- Medication adherence is critical for clinical trial efficacy and safety.
- Current adherence monitoring methods like pill counts and plasma assessments have limitations.
- Non-invasive monitoring without breaking trial blind is desirable.
Purpose of the Study:
- To clinically implement 15 mg acetazolamide (ACZ) as an adherence marker excipient.
- To confirm ACZ does not accumulate during adherence and to develop urinary cutoffs for nonadherence.
- To assess the reliability and sensitivity of ACZ for monitoring medication consumption in clinical trials.
Main Methods:
- 15 mg acetazolamide (ACZ) was administered as an adherence marker excipient in distinct patient cohorts.
- Urinary ACZ concentrations were measured and analyzed for accumulation during adherence.
- Urinary ACZ cutoffs were developed and assessed for detecting nonadherence, including creatinine normalization.
- Urinary ACZ excretion kinetics and half-life were determined during nonadherent phases.
Main Results:
- ACZ did not accumulate in urine during 18-20 days of adherence.
- A creatinine-normalized cutoff (1,376 ng/mg ACZ) accurately detected nonadherence, outperforming an absolute concentration cutoff.
- Urinary ACZ elimination during nonadherence was reproducible with low variability across trials.
- ACZ excretion followed first-order kinetics with a half-life of approximately 2.0 days and remained quantifiable for 14 days.
Conclusions:
- 15 mg acetazolamide (ACZ) serves as a reliable adherence marker excipient in clinical efficacy trials.
- Creatinine-normalized urinary ACZ levels provide a sensitive and accurate method for detecting nonadherence.
- This non-invasive approach allows for reliable confirmation of medication consumption and monitoring of adherence without compromising trial blinding.
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