Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
TGelBio Co., Ltd., Seoul, South Korea.
Clin Exp Pharmacol Physiol. 2021 Jun;48(6):932-937. doi: 10.1111/1440-1681.13492. Epub 2021 Mar 24.
Therapeutic agents with a short half-life need to be administered frequently to achieve sustained and effective concentrations. This could be accomplished using sustained drug delivery technology. PF-72 (TGel Bio, Inc., Seoul, Korea) is a drug delivery system based on a powder obtained from lyophilisation of a reverse thermal hydrogel, which could assist in achieving prolonged pain relief if mixed with an anaesthetic and injected into the incision site following surgery. The pharmacokinetic parameters related to the absorption of the local anaesthetic ropivacaine delivered using this hydrogel were quantified. Ten rats were divided into two groups (n = 5 each), and equal doses (4 mg/kg) of different formulations were subcutaneously injected into the abdomen. The experimental group received PF-72 mixed with 0.75% ropivacaine, and the control group received 0.75% ropivacaine. Blood was collected at specific times to measure the plasma concentration of ropivacaine. Population pharmacokinetic analysis was performed using NONMEM VII level 4 (ICON Development Solutions, Dublin, Ireland). The one-compartment absorption model, which combines zero-order absorption and first-order absorption, was used to describe the change in ropivacaine plasma concentration over time. The type of formulation was a significant covariate for zero-order absorption duration (experimental group, 92.9 min; control group, 60.5 min). The addition of PF-72 to 0.75% ropivacaine increased the duration of absorption into the blood, suggesting a longer lasting effect of the analgesic injected into the surgical wound.
治疗剂半衰期较短，需要频繁给药才能达到持续有效的浓度。这可以通过持续药物递送技术来实现。PF-72（TGel Bio，Inc.，韩国首尔）是一种基于冻干反向温敏水凝胶粉末的药物递送系统，如果与麻醉剂混合并在手术后注入切口部位，可能有助于实现延长的疼痛缓解。定量了使用这种水凝胶递送局部麻醉药罗哌卡因的吸收的药代动力学参数。将 10 只大鼠分为两组（每组 n=5），并将不同制剂的等量（4mg/kg）皮下注射到腹部。实验组接受 PF-72 与 0.75%罗哌卡因混合，对照组接受 0.75%罗哌卡因。在特定时间采集血液以测量罗哌卡因的血浆浓度。使用 NONMEM VII 级别 4（ICON Development Solutions，爱尔兰都柏林）进行群体药代动力学分析。将零级吸收和一级吸收相结合的单室吸收模型用于描述罗哌卡因血浆浓度随时间的变化。制剂类型是零级吸收持续时间的显著协变量（实验组 92.9 分钟；对照组 60.5 分钟）。将 PF-72 添加到 0.75%罗哌卡因中增加了血液吸收的持续时间，表明注入手术伤口的镇痛剂的作用持续时间更长。
