Altered Pharmacokinetics of Ropivacaine in Patients Undergoing Laparoscopic Major Hepatectomy

<b>Background/Objectives:</b> Ropivacaine is primarily metabolized by the liver. High doses of ropivacaine, combined with altered pharmacokinetics due to hepatectomy, raise concerns about potential drug toxicity. We investigated the impact of LMH (laparoscopic major hepatectomy) on the p...

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Main Authors: Jun Zhang, Hongyuan Lv, Jiliang Shen, Zhichao Ai, Minjun Liu, Xiaorui Liu, Tieshuai Liu, Bo Shen, Hong Yu, Xin Yu
Format: Article
Language:English
Published: MDPI AG 2025-03-01
Series:Pharmaceutics
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Online Access:https://www.mdpi.com/1999-4923/17/3/386
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author Jun Zhang
Hongyuan Lv
Jiliang Shen
Zhichao Ai
Minjun Liu
Xiaorui Liu
Tieshuai Liu
Bo Shen
Hong Yu
Xin Yu
author_facet Jun Zhang
Hongyuan Lv
Jiliang Shen
Zhichao Ai
Minjun Liu
Xiaorui Liu
Tieshuai Liu
Bo Shen
Hong Yu
Xin Yu
author_sort Jun Zhang
collection DOAJ
description <b>Background/Objectives:</b> Ropivacaine is primarily metabolized by the liver. High doses of ropivacaine, combined with altered pharmacokinetics due to hepatectomy, raise concerns about potential drug toxicity. We investigated the impact of LMH (laparoscopic major hepatectomy) on the pharmacokinetics of high-dose ropivacaine. <b>Methods:</b> Ten patients undergoing LMH received a BD-TAP (bilateral dual transversus abdominis plane) block with a high dose of ropivacaine (3 mg·kg<sup>−1</sup> in 60 mL). Plasma concentrations of total and free ropivacaine and AAG (alpha-1 acid glycoprotein) levels were measured. Liver volumes were calculated using three-dimensional liver reconstruction technology. <b>Results:</b> The peak total ropivacaine concentration occurred 45 min after the block, reaching 2031.5 (876.0) ng·mL<sup>−1</sup>, with a tendency to exceed the toxicity threshold in patients with a CFLV (cut functional liver volume) exceeding 199.24 mL or a CFLV/TFLV (total functional liver volume) ratio surpassing 18.61%. The peak free ropivacaine concentration, 111.5 (31.3) ng·mL<sup>−1</sup>, was observed 90 min after the block, potentially exceeding the toxicity threshold when CFLV exceeded 452.33 mL or the CFLV/TFLV ratio was greater than 42.16%. Plasma AAG levels increased approximately 1.5 times within 24 h, from 1519.7 (422.6) μg·mL<sup>−1</sup> preoperatively to 2253.6 (460.4) μg·mL<sup>−1</sup> postoperatively, effectively reducing the toxicity risk associated with free ropivacaine. <b>Conclusions:</b> Preoperative administration of high-dose ropivacaine can be safely utilized in patients undergoing major hepatectomy. The increased plasma AAG concentration due to surgical stress reduces free ropivacaine levels, enhancing patient tolerance to the drug. The CFLV and CFLV/TFLV ratio may be supplementary indicators for predicting ropivacaine toxicity.
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series Pharmaceutics
spelling doaj-art-c5d02c4b94c04530a49cb47d6c1b8a592025-08-20T03:43:40ZengMDPI AGPharmaceutics1999-49232025-03-0117338610.3390/pharmaceutics17030386Altered Pharmacokinetics of Ropivacaine in Patients Undergoing Laparoscopic Major HepatectomyJun Zhang0Hongyuan Lv1Jiliang Shen2Zhichao Ai3Minjun Liu4Xiaorui Liu5Tieshuai Liu6Bo Shen7Hong Yu8Xin Yu9Department of Anesthesiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310058, ChinaDepartment of Anesthesiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310058, ChinaDepartment of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310058, ChinaDepartment of Anesthesiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310058, ChinaDepartment of Nursing Education, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310058, ChinaDepartment of Radiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310058, ChinaDepartment of Anesthesiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310058, ChinaDepartment of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310058, ChinaDepartment of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310058, ChinaDepartment of Anesthesiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310058, China<b>Background/Objectives:</b> Ropivacaine is primarily metabolized by the liver. High doses of ropivacaine, combined with altered pharmacokinetics due to hepatectomy, raise concerns about potential drug toxicity. We investigated the impact of LMH (laparoscopic major hepatectomy) on the pharmacokinetics of high-dose ropivacaine. <b>Methods:</b> Ten patients undergoing LMH received a BD-TAP (bilateral dual transversus abdominis plane) block with a high dose of ropivacaine (3 mg·kg<sup>−1</sup> in 60 mL). Plasma concentrations of total and free ropivacaine and AAG (alpha-1 acid glycoprotein) levels were measured. Liver volumes were calculated using three-dimensional liver reconstruction technology. <b>Results:</b> The peak total ropivacaine concentration occurred 45 min after the block, reaching 2031.5 (876.0) ng·mL<sup>−1</sup>, with a tendency to exceed the toxicity threshold in patients with a CFLV (cut functional liver volume) exceeding 199.24 mL or a CFLV/TFLV (total functional liver volume) ratio surpassing 18.61%. The peak free ropivacaine concentration, 111.5 (31.3) ng·mL<sup>−1</sup>, was observed 90 min after the block, potentially exceeding the toxicity threshold when CFLV exceeded 452.33 mL or the CFLV/TFLV ratio was greater than 42.16%. Plasma AAG levels increased approximately 1.5 times within 24 h, from 1519.7 (422.6) μg·mL<sup>−1</sup> preoperatively to 2253.6 (460.4) μg·mL<sup>−1</sup> postoperatively, effectively reducing the toxicity risk associated with free ropivacaine. <b>Conclusions:</b> Preoperative administration of high-dose ropivacaine can be safely utilized in patients undergoing major hepatectomy. The increased plasma AAG concentration due to surgical stress reduces free ropivacaine levels, enhancing patient tolerance to the drug. The CFLV and CFLV/TFLV ratio may be supplementary indicators for predicting ropivacaine toxicity.https://www.mdpi.com/1999-4923/17/3/386alpha-1 acid glycoproteinbilateral dual transversus abdominis plane blocklaparoscopic major hepatectomylocal anesthetic toxicityropivacaine
spellingShingle Jun Zhang
Hongyuan Lv
Jiliang Shen
Zhichao Ai
Minjun Liu
Xiaorui Liu
Tieshuai Liu
Bo Shen
Hong Yu
Xin Yu
Altered Pharmacokinetics of Ropivacaine in Patients Undergoing Laparoscopic Major Hepatectomy
Pharmaceutics
alpha-1 acid glycoprotein
bilateral dual transversus abdominis plane block
laparoscopic major hepatectomy
local anesthetic toxicity
ropivacaine
title Altered Pharmacokinetics of Ropivacaine in Patients Undergoing Laparoscopic Major Hepatectomy
title_full Altered Pharmacokinetics of Ropivacaine in Patients Undergoing Laparoscopic Major Hepatectomy
title_fullStr Altered Pharmacokinetics of Ropivacaine in Patients Undergoing Laparoscopic Major Hepatectomy
title_full_unstemmed Altered Pharmacokinetics of Ropivacaine in Patients Undergoing Laparoscopic Major Hepatectomy
title_short Altered Pharmacokinetics of Ropivacaine in Patients Undergoing Laparoscopic Major Hepatectomy
title_sort altered pharmacokinetics of ropivacaine in patients undergoing laparoscopic major hepatectomy
topic alpha-1 acid glycoprotein
bilateral dual transversus abdominis plane block
laparoscopic major hepatectomy
local anesthetic toxicity
ropivacaine
url https://www.mdpi.com/1999-4923/17/3/386
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