OP.2B.01] DEVELOPMENT OF A DRIED BLOOD SPOT (DBS) BASED MEASUREMENT OF ANTIHYPERTENSIVE DRUG LEVELS TO ASSESS ADHERENCE

Abstract

Objective: Resistant hypertension, defined as uncontrolled blood pressure despite a medication regimen of antihypertensive drugs from at least three classes including a diuretic, is a common health issue leading to suboptimal cardiovascular prevention. 11–16% of patients with hypertension fulfill this definition. The majority of these patients have a problem with adherence to their medication, explaining their assumed resistance to therapy. Proving and, more importantly, improving adherence is of major importance to reduce disease burden and costs. We aimed to develop a method to measure drug levels of antihypertensive drugs in a dried blood spot (DBS) obtained by a finger prick. Design and method: We developed a rapid multimethod using UPLC-MS/MS for eight antihypertensive drugs and four active metabolites in plasma and DBS. The most used drugs of four classes were chosen: enalapril, perindopril, losartan, valsartan, hydrochlorothiazide, spironolactone, amlodipine and nifedipine. Validation using academic standards in donor blood showed high linearity between plasma and DBS measurements. For further clinical validation, we measured peak and trough levels in both DBS and plasma from patients using at least two of the drugs for which the DBS test was developed. We aimed to select for each drug at least ten patients assumed to be adherent based on blood pressure levels below target. Results: Currently, for 29 patients peak and trough levels were collected for at least two antihypertensives. Agreement between plasma and DBS measurements looks promising so far. Remarkably, peak and trough levels for all drugs varied considerably between patients. For instance trough levels of valsartan when dosed 320 mg qd were in a range of 283–1138 μg/l. Trough levels of hydrochlorothiazide were undetectable as expected, while the active metabolite of spironolactone canrenon was still above the lower limit of quantification. Conclusions: Therapeutic drug monitoring using DBS can be a convenient method to monitor drug adherence. The advantage of DBS above plasma measurement is that sampling can take place at the exact moment the increased blood pressure is measured. This diminishes the risk of white coat adherence as seen when an additional visit to the blood sampling unit is needed.