An in vivo porcine evaluation of the safety, bioavailability, and tissue penetration of a ketorolac drug-eluting ureteral stent designed to improve comfort.

BACKGROUND AND PURPOSE

Ureteral stents often cause significant patient morbidity that can be difficult to treat. Drug-eluting stent technology allows the local delivery of a drug. Our previous work demonstrated that ketorolac instilled intravesically at the time of ureteral stent insertion significantly decreased flank pain compared with controls. We sought to determine the safety of a novel ketorolac-eluting ureteral stent.

MATERIALS AND METHODS

A total of 92 Yorkshire pigs were randomized to 1 of 5 groups. The oral control group consisted of 12 animals with transurethrally inserted control ureteral stents and 5 days of oral ketorolac. Twenty animals in each of the remaining groups received a control stent, or 15%, 13%, or 7% ketorolac-loaded stents. Ketorolac levels were measured in plasma, urine, and tissue sampled from ureters, bladder, kidneys, and liver using high performance liquid chromatography. Necropsies were performed to evaluate tissue pathology.

RESULTS

The majority of ketorolac was released within the first 30 days. The highest levels of ketorolac in plasma, kidney, and liver occurred in the oral control group. The highest levels of ketorolac found in ureteral and bladder tissues occurred in the ketorolac-stent groups in a dose-dependent fashion. No adverse events were noted in any of the ketorolac-stent groups. Gastric ulcerations were identified only in the oral control group. No abnormalities were identified in any other internal organs in any group.

CONCLUSIONS

The use of ketorolac-eluting ureteral stents has proven to be safe in a porcine model. The ketorolac-stent group had less than 12% of the ketorolac concentration in plasma, kidney, and liver tissues compared with the oral ketorolac group. Ureteral tissues displayed the highest levels of ketorolac. Clinical studies are needed to determine if ketorolac-elution reduces stent symptoms.