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

Ji Yeon Bang, Sugeun Nam, Chang Soon Hwang, Eun Kyung Lee, Byung Moon Choi

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)932-937
Number of pages6
JournalClinical and Experimental Pharmacology and Physiology
Volume48
Issue number6
DOIs
StatePublished - Jun 2021

Bibliographical note

Publisher Copyright:
© 2021 John Wiley & Sons Australia, Ltd

Keywords

  • absorption
  • model
  • pharmacokinetics
  • population analysis
  • ropivacaine

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