Details

Autor(en) / Beteiligte

• Cui, Huixin
• Lyu, Lihong
• Bian, Jing
• Xu, Shan
• Chen, Rui
• Cai, Chunxiao
• Chen, Yao
• Xu, Zhi-ru

Titel

LC-MS/MS quantification of ropivacaine and local analgesic and adverse effects of Long-acting Ropivacaine Injection based on pharmacokinetic-pharmacodynamic modelling in Bama minipigs

Ist Teil von

• Journal of chromatography. B, Analytical technologies in the biomedical and life sciences, 2023-05, Vol.1223, p.123716-123716, Article 123716

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2023

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• •An LC-MS/MS method to quantify ropivacaine in minipig plasma was developed. And the sensitive and robust method was successfully used in a minipig PK-PD study.•Long-acting Ropivacaine Injection were examined based on PK-PD model.•Long-acting Ropivacaine Injection has longer-lasting efficacy at lower concentrations.•The PK-PD model revealed a direct relationship between plasma ropivacaine concentration and MWT.•The PK-PD model behaved good prediction ability. The local analgesic efficacy and adverse effects of a new Long-acting Ropivacaine formulation were examined based on pharmacokinetic-pharmacodynamic (PK-PD) modelling in Bama minipigs. 24 Bama minipigs, 12 males and 12 females, were randomly and equally divided into the following treatment groups: normal saline injection, drug vehicle injection, Long-acting Ropivacaine Injection and Ropivacaine Hydrochloride Injection. After routine disinfection, a skin incision about 3 cm long and 3 cm deep was produced in the leg of each pig, and mechanical withdrawal threshold (MWT) measured at various times pre- and post-injection as an index of analgesia against incision pain. Plasma ropivacaine concentrations were also measured at the same times using a novel liquid chromatography-tandem mass spectroscopy (LC-MS/MS) method. Minipigs were sacrificed 24 h post-injection and hearts collected for drug concentration measurements by LC-MS/MS. The LC-MS/MS method demonstrated high sensitivity, linearity and precision. The Long-acting Ropivacaine formulation produced a longer analgesic effect (∼12 h) at a lower plasma concentration than Ropivacaine Hydrochloride (∼4h), suggesting a better side-effects profile. A PK-PD model revealed a direct relationship between plasma ropivacaine concentration and MWT, with peak analgesia at about 1000 ng/mL and behaved good prediction ability. Long-acting Ropivacaine Injection is a superior local anaesthetic-analgesic treatment due to longer-lasting efficacy at lower concentrations compared to Ropivacaine Hydrochloride, which will reduce the risk of side effects such as cardiotoxicity.