Population Pharmacokinetic Modeling of Diltiazem in Chinese Renal Transplant Recipients

Guan, Xiangdong; Li, Dai-Yang; Wu, Yin; Ding, Junjie; Zhou, Lingyun; Wang, Jianglin; Ma, Rongrong; Zuo, Xiaoxia

doi:10.1007/s13318-017-0425-y

Cited by 1 publication

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“…However, our finding could be explained by the fact that sufentanil binding is affected mainly by the plasma concentration of α1-acid glycoprotein, and not by the total plasma protein level. Low total protein levels might reflect impaired hepatic function, which could produce low apparent volumes of distribution [37]. We want to highlight that our results are observatory and further studies are needed to fully uncover the relationship between total protein level and volume of distribution.…”

Section: Discussionmentioning

confidence: 95%

Population pharmacokinetics of intravenous sufentanil in critically ill patients supported with extracorporeal membrane oxygenation therapy

et al. 2019

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Background Sufentanil is commonly used for analgesia and sedation during extracorporeal membrane oxygenation (ECMO). Both ECMO and the pathophysiological changes derived from critical illness have significant effects on the pharmacokinetics (PK) of drugs, yet reports of ECMO and sufentanil PK are scarce. Here, we aimed to develop a population PK model of sufentanil in ECMO patients and to suggest dosing recommendations. Methods This prospective cohort PK study included 20 patients who received sufentanil during venoarterial ECMO (VA-ECMO). Blood samples were collected for 96 h during infusion and 72 h after cessation of sufentanil. A population PK model was developed using nonlinear mixed effects modelling. Monte Carlo simulations were performed using the final PK parameters with two typical doses. Results A two-compartment model best described the PK of sufentanil. In our final model, increased volume of distribution and decreased values for clearance were reported compared with previous PK data from non-ECMO patients. Covariate analysis showed that body temperature and total plasma protein level correlated positively with systemic clearance (CL) and peripheral volume of distribution (V2), respectively, and improved the model. The parameter estimates of the final model were as follows: CL = 37.8 × EXP (0.207 × (temperature − 36.9)) L h −1 , central volume of distribution (V1) = 229 L, V2 = 1640 × (total plasma protein/4.5) 2.46 L, and intercompartmental clearance ( Q ) = 41 L h −1 . Based on Monte Carlo simulation results, an infusion of 17.5 μg h −1 seems to reach target sufentanil concentration (0.3–0.6 μg L −1 ) in most ECMO patients except hypothermic patients (33 °C). In hypothermic patients, over-sedation, which could induce respiratory depression, needs to be monitored especially when their total plasma protein level is low. Conclusions This is the first report on a population PK model of sufentanil in ECMO patients. Our results suggest that close monitoring of the body temperature and total plasma protein level is crucial in ECMO patients who receive sufentanil to provide effective analgesia and sedation and promote recovery. Trial registration Clinicaltrials.gov NCT02581280 , December 1st, 2014.

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Section: Discussionmentioning

confidence: 95%

Population pharmacokinetics of intravenous sufentanil in critically ill patients supported with extracorporeal membrane oxygenation therapy

et al. 2019

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Population Pharmacokinetic Modeling of Diltiazem in Chinese Renal Transplant Recipients

Abstract: A PopPK model of diltiazem is established in Chinese renal transplant recipients and it will provide relevant pharmacokinetic parameters of diltiazem for further pharmacokinetic interaction study.

Cited by 1 publication

References 32 publications

Population pharmacokinetics of intravenous sufentanil in critically ill patients supported with extracorporeal membrane oxygenation therapy

Population pharmacokinetics of intravenous sufentanil in critically ill patients supported with extracorporeal membrane oxygenation therapy

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