Favorable pharmacokinetics of biolimus A9 after deployment of Nobori stent for coronary artery disease: insights from Nobori PK study in Japanese subjects

Abstract

The Nobori stent is a new drug-eluting stent (DES) with biodegradable polymer coating limited to the abluminal side of stents. Biolimus A9 is a novel sirolimus derivative specifically developed for DES, and polymer load 15.6 μg of biolimus A9 per 1 mm of stent. A non-randomized multicenter trial was conducted in Japan. Twenty-two de novo lesions were treated by Nobori stents and biolimus A9 concentration in whole blood was serially measured at 14 predetermined time points using a validated chromatography-tandem mass spectrometry (LC-MS/MS) assay. The C max was 85.3 ± 37.9 pg/mL (min-max 46.7-169 pg/mL) in the 18 mm cohort and 198 ± 81 pg/mL (min-max 82.5-365 pg/mL) in the ≥ 28 mm cohort and no early or late bursts of biolimus A9 release were documented. After 4 weeks, no measurable concentration of biolimus A9 was observed in any patient. Estimated AUC0-t was 1.12 ± 1.16 ng/mL h in the 18 mm group, and 5.93 ± 4.41 ng/mL h for the ≥ 28 mm group. A significant association between loaded biolimus A9 dose adjusted by patient weight and pharmacokinetic parameters was observed. The systemic exposure of biolimus A9 eluting from the Nobori stent was low and proportional to the loaded amount of biolimus A9, and clearance from the blood was rapid. These findings suggest that the Nobori stent is feasible and safe. Systemic lower exposure of biolimus A9 after Nobori stent implantation may have beneficial effects on stent endothelialization.