Fixed dosing of kukoamine B in sepsis patients: Results from population pharmacokinetic modelling and simulation

Wang, Huanhuan; Wang, Teng; Hu, Xiaoyun; Deng, Chonghai; Jiang, Ji; Qin, Hanyu; Dong, Kai; Chen, Shuai; Jin, Chunyan; Zhao, Qian; Du, Bin; Hu, Pei

doi:10.1111/bcp.15342

Cited by 3 publications

(1 citation statement)

References 25 publications

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“…In addition, the choice of nalbuphine dosage regimens is also an issue worth to be discussed. Wang et al (2022) found that the PK variability of the drug was lower for fixed-dose dosage regimens than that for weight-based dosage regimens. Previous studies had shown that weight of neonates and children is a significant factor affecting nalbuphine PK behavior ( Jacqz-Aigrain et al, 2003 ; Bressolle et al, 2011 ).…”

Section: Introductionmentioning

confidence: 97%

Population pharmacokinetics of nalbuphine in patients undergoing general anesthesia surgery

Nie

Gao

et al. 2023

Front. Pharmacol.

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Purpose: The aim of this study was to build a population pharmacokinetics (PopPK) model of nalbuphine and to estimate the suitability of bodyweight or fixed dosage regimen.Method: Adult patients who were undergoing general anesthetic surgery using nalbuphine for induction of anesthesia were included. Plasma concentrations and covariates information were analyzed by non-linear mixed-effects modeling approach. Goodness-of-fit (GOF), non-parametric bootstrap, visual predictive check (VPC) and external evaluation were applied for the final PopPK model evaluation. Monte Carlo simulation was conducted to assess impact of covariates and dosage regimens on the plasma concentration to nalbuphine.Results: 47 patients aged 21–78 years with a body weight of 48–86 kg were included in the study. Among them, liver resection accounted for 14.8%, cholecystectomy for 12.8%, pancreatic resection for 36.2% and other surgeries for 36.2%. 353 samples from 27 patients were enrolled in model building group; 100 samples from 20 patients were enrolled in external validation group. The results of model evaluation showed that the pharmacokinetics of nalbuphine was adequately described by a two-compartment model. The hourly net fluid volume infused (HNF) was identified as a significant covariate about the intercompartmental clearance (Q) of nalbuphine with objective function value (OFV) decreasing by 9.643 (p < 0.005, df = 1). Simulation results demonstrated no need to adjust dosage based on HNF, and the biases of two dosage methods were less than 6%. The fixed dosage regimen had lower PK variability than the bodyweight regimen.Conclusion: A two-compartment PopPK model adequately described the concentration profile of nalbuphine intravenous injection for anesthesia induction. While HNF can affect the Q of nalbuphine, the magnitude of the effect was limited. Dosage adjustment based on HNF was not recommended. Furthermore, fixed dosage regimen might be better than body weight dosage regimen.

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Section: Introductionmentioning

confidence: 97%

Population pharmacokinetics of nalbuphine in patients undergoing general anesthesia surgery

Nie

Gao

et al. 2023

Front. Pharmacol.

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First-in-Human Safety, Tolerability, and Pharmacokinetics of Single-Dose Kukoamine B Mesylate in Healthy Subjects: A Randomized, Double-Blind, Placebo-Controlled Phase I Study

Liu,

Zhao,

Yuan

et al. 2024

Infect Dis Ther

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The Effect of the Root Bark of Lycium chinense (Lycii Radicis Cortex) on Experimental Periodontitis and Alveolar Bone Loss in Sprague-Dawley Rats

Yang,

Song,

Lee

et al. 2024

Antioxidants

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Lycii Radicis Cortex (LRC), the dried root bark of Lycium chinese Mill., has traditionally been used as a medicinal herb in East Asia to treat fever and hyperhidrosis. In the present study, we investigated the effects of LRC extract on ligation-induced experimental periodontitis and associated alveolar bone loss in rats. Twenty-four hours after ligation placement, LRC was orally administered once daily for 10 days. Firstly, LRC administration inhibited anaerobic bacterial proliferation and inflammatory cell infiltration in gingival tissues. Additionally, LRC exhibited anti-inflammatory effects by reducing the expression of inflammatory mediators, including prostaglandin E2, interleukin-1β, and tumor necrosis factor-α. LRC treatment also downregulated mRNA expression of these inflammatory mediators in lipopolysaccharide-stimulated RAW 264.7 cells by inhibiting the mitogen-activated protein kinases and nuclear factor-κB (NF-κB) signaling pathways. Furthermore, LRC showed an antioxidant effect by decreasing the malondialdehyde level and inducible nitric oxide synthase activity in gingival tissues. Moreover, LRC effectively prevented the connective tissue degradation by inhibiting matrix metalloproteinase-8 expression and the loss of collagen-occupied areas in gingival tissues. LRC also decreased the receptor activator of NF-κB ligand/osteoprotegerin (RANKL/OPG) ratio, as well as the number and occupied areas of osteoclasts on the alveolar bone surface, thereby inhibiting alveolar bone loss. In summary, these findings suggest that LRC is a promising medicinal herb for alleviating periodontitis and related alveolar bone loss through its antimicrobial, anti-inflammatory, and antioxidant properties.

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Fixed dosing of kukoamine B in sepsis patients: Results from population pharmacokinetic modelling and simulation

Cited by 3 publications

References 25 publications

Population pharmacokinetics of nalbuphine in patients undergoing general anesthesia surgery

Population pharmacokinetics of nalbuphine in patients undergoing general anesthesia surgery

First-in-Human Safety, Tolerability, and Pharmacokinetics of Single-Dose Kukoamine B Mesylate in Healthy Subjects: A Randomized, Double-Blind, Placebo-Controlled Phase I Study

The Effect of the Root Bark of Lycium chinense (Lycii Radicis Cortex) on Experimental Periodontitis and Alveolar Bone Loss in Sprague-Dawley Rats

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