Population pharmacokinetic analysis of ropivacaine extended‐release from a temperature‐responsive hydrogel in rats

Abstract

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.

A Prospective, Single-Center, Single-Blind, Randomized, Confirmatory, Controlled Trial to Assess the Efficacy and Safety of PF-72 Combined with 0.75% Ropivacaine Hydrochloride in Patients Undergoing Single-Level Lumbar Discectomy

“…Bang JY, et al performed an animal experiment to assess the population pharmacokinetic profile of 0.75% ropivacaine combined with PF-72, thus showing that there was an increase in the duration of absorption in the blood. These authors suggested that PF-72 combined with 0.75% ropivacaine might sustain effects of 0.75% ropivacaine at the surgical site [14]. Moreover, Oh KS, et al conducted a preclinical study to assess the pharmacokinetic, distribution and efficacy of PF-72 containing 0.75% ropivacaine for extended relief of postoperative pain by allowing the prolonged release of ropivacaine.…”