부산대학교 도서관

Background: The pharmacokinetic properties and clinical advantages of the local anesthetic chloroprocaine are well known. Here, we studied the pharmacokinetic profile of a new hydrogel device loaded with chloroprocaine to investigate the potential advantages of this new strategy for postoperative pain (POP) relief. Materials and methods: We performed both in vitro and in vivo analyses by considering plasma samples of four piglets receiving slow-release chloroprocaine. To quantify chloroprocaine and its inactive metabolite 4-amino-2-chlorobenzoic acid (ACBA), a HPLC-tandem mass spectrometry (HPLC-MS/MS) analytical method was used. Serial blood samples were collected over 108 hours, according to the exposure time to the device. Results: Chloroprocaine was consistently found to be below the lower limit of quantification, even though a well-defined peak was observed in every chromatogram at an unexpected retention time. Concerning ACBA, we found detectable plasma concentrations between T0 and T12h, with a maximum plasma concentration ([C.sub.max]) observed 3 hours after the device application. In the in vitro analyses, the nanogel remained in contact with plasma at 37[degrees]C for 90 minutes, 3 hours, 1 day, and 7 days. Chloroprocaine [C.sub.max] was identified 1 day following exposure and [C.sub.min] after 7 days, respectively. Additionally, ACBA reached the [C.sub.max] following 7 days of exposure. Conclusion: A thorough review of the literature indicates that this is the first study analyzing both in vivo and in vitro pharmacokinetic profiles of a chloroprocaine hydrogel device and is considered as a pilot study on the feasibility of including this approach to the management of POP. Keywords: postoperative outcome, hydrogel device, chloroprocaine, ACBA, pharmacokinetics
Introduction The mechanism of local anesthetics (LAs) in blocking the transmission of painful stimuli to the brain is well known. (1) Chloroprocaine, an ester-type LA, is less cardiotoxic than most [...]