Pharmacokinetic Profile of Everolimus Eluted From the Esprit BTK Scaffold: A LIFE-BTK Pharmacokinetics Substudy

The most severe manifestation of peripheral artery disease, chronic limb-threatening ischemia, is associated with limited treatment options for below-the-knee (BTK) arteries. The Esprit BTK everolimus-eluting resorbable scaffold system (Abbott), now approved by the U.S. Food and Drug Administration for the treatment of infrapopliteal lesions in patients with chronic limb-threatening ischemia, was evaluated in the LIFE-BTK randomized controlled trial. LIFE-BTK included a nonrandomized substudy evaluating the pharmacokinetic (PK) profile of everolimus eluted from the scaffold.

The PK substudy enrolled 9 subjects across 2 treatment groups (with or without drug-coated balloon use for inflow lesion and/or nontarget lesion treatment). Blood concentration-time profiles and PK parameters were determined at multiple time points and compared with prior PK results from the Absorb bioresorbable vascular scaffold.

The number of implanted scaffolds averaged 6.6 ± 0.9, with a total length ranging from 180 to 256 mm and an everolimus dose ranging from 1397 to 2074 μg per subject. The last time point at which everolimus could be quantified ranged from 168 to 720 hours, and in most cases, the blood concentrations dropped below the lower limit of quantification (0.1 ng/mL) before 720 hours. Peak blood everolimus levels were followed by a biexponential decline, with terminal phase half-life ranging from 65.6 to 211.2 hours. A regression analysis using dose-normalized maximum blood everolimus concentration and area under the blood concentration-time curve confirmed similar everolimus exposure across the treatment groups.

The present substudy assessed the PK of everolimus delivered by Esprit BTK in the planned treatment of narrowed infrapopliteal lesions. This study confirms that the PK profile of everolimus eluted from the Esprit BTK scaffold results in limited systemic exposure and is considered to be safe and well tolerated.