Population Pharmacokinetic-Pharmacodynamic Modeling of Ropivacaine in Spinal Anesthesia

Djerada, Zoubir; Féliu, Catherine; Cazaubon, Yoann; Smati, Faouzi; Gomis, Philippe; Guerrot, Dominique; Fernandes, Olivier; Malinovsky, Jean‐Marc

doi:10.1007/s40262-017-0617-2

Cited by 31 publications

(23 citation statements)

References 50 publications

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“…Therefore, it is of great significance to identify the effects and side effects of various methods of labor analgesia, for that can greatly contribute to the selection of clinical analgesic methods, the reduction of cesarean section rate and the improvement of maternal and newborn health . Epidural anesthesia combined with the use of opioids is currently a commonly used approach for analgesia . As one of local anesthetic drugs belonging to the amide class, ropivacaine is the preferred choice for epidural anesthesia since it has less negative effects on the central nervous system and the heart .…”

Section: Discussionmentioning

confidence: 99%

Dexmedetomidine versus sufentanil with high‐ or low‐concentration ropivacaine for labor epidural analgesia: A randomized trial

Cheng

Zhang

et al. 2019

J of Obstet and Gynaecol

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Aim: To study analgesic effects of dexmedetomidine or sufentanil, both combined with ropivacaine, in epidural analgesia during labor. Methods: We recruited 160 primigravidae with full-term pregnancy who received epidural anesthesia during labor and randomized them into four groups to receive epidural administration of ropivacaine combined with sufentanil (RS 1 and RS 2 groups) or with dexmedetomidine (RD 1 and RD 2 groups). Systolic blood pressure, diastolic blood pressure and heart rate before anesthesia (T 1 ), 15 min after anesthesia induction (T 2 ), on delivery (T 3 ) and 2 h postpartum (T 4 ), together with visual analogue scale scores, Bromage scores, Ramsay scores, adverse reactions during analgesia and urinary retention at 6 and 24 h postpartum were recorded; the pH, PCO 2 and PO 2 of umbilical cord arterial blood and Apgar scores at 1, 5 and 10 min after childbirth were assessed. Results: RS 1 group had significantly lower systolic blood pressure, diastolic blood pressure and heart rate than RD 1 group at T 2 and T 3 (all P < 0.05), but not at T1. At T 2 and T 3 , the other three groups were lower than RS 2 group in visual analogue scale and Ramsay scores (all P < 0.05). After childbirth, RD 2 group had significantly higher PO 2 result than other three groups (P < 0.05). At 6 h postpartum, RD 2 group had significantly fewer cases of urinary retention than RD 1 and RS 1 groups (both P < 0.05). Conclusion: A relatively low concentration of ropivacaine, combined with dexmedetomidine, is better in analgesia during labor.

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Section: Discussionmentioning

confidence: 99%

Dexmedetomidine versus sufentanil with high‐ or low‐concentration ropivacaine for labor epidural analgesia: A randomized trial

Cheng

Zhang

et al. 2019

J of Obstet and Gynaecol

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“…In the final model, the 95% confidence interval of each parameter was determined from 1000 nonparametric bootstraps based on resampling [18,19] while using R package Rsmlx [20].…”

Section: Model Qualification Processmentioning

confidence: 99%

“…Multicollinearity was checked while using collinearity statistics (variance inflation factor of approximately 1). Final multiple linear model was externally validated, using the cross-validation technique [19]. Multivariate analysis was performed with R 3.1.4 (The R Foundation for Statistical Computing, http://www.r-project.org).…”

Section: Hl Comparison After Switchmentioning

confidence: 99%

Real Life Population Pharmacokinetics Modelling of Eight Factors VIII in Patients with Severe Haemophilia A: Is It Always Relevant to Switch to an Extended Half-Life?

et al. 2020

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We retrospectively analysed the data files of 171 adults and 87 children/adolescents with severe haemophilia, except for 14 patients (moderate; minor) (1), to develop a global population pharmacokinetic (PK) model for eight factors VIII (FVIII) that could estimate individual PK parameters for targeting the desired level of FVIII activity (FVIII:C); and (2) to compare half-life (HL) in patients switching from a standard half-life (SHL) to an extended half-life (EHL) and evaluate the relevance of the switch. One-stage clotting assay for the measurement of FVIII activity (FVIII:C, IU/mL) was used for population PK modelling. The software, Monolix version 2019R1, was used for non-linear mixed-effects modelling. A linear two-compartment model best described FVIII:C. The estimated PK parameters (between-subject variability) were: 2640 mL (23.2%) for volume of central compartment (V1), 339 mL (46.8%) for volume of peripheral compartment (V2), 135 mL/h for Q (fixed random effect), and 204 mL/h (34.9%) for clearance (Cl). Weight, age, and categorical covariate EHL were found to influence Cl and only weight for V1. This model can be used for all of the FVIII cited in the study. Moreover, we demonstrated, in accordance with previous studies, that Elocta had longer half-life (EHL) than SHL (mean ratio: 1.48) as compared to Advate, Factane, Kogenate, Novoeight, and Refacto.

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“…Bonferroni correction was applied for multiple comparisons. All p-values were two-tailed with statistical significance indicated by a value of p < 0.05 [77,78].…”

Section: Statisticsmentioning

confidence: 99%

Ticagrelor Prevents Endothelial Cell Apoptosis through the Adenosine Signalling Pathway in the Early Stages of Hypoxia

et al. 2020

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Background: Several studies have reported the beneficial effects of anti-platelet drugs in cardioprotection against ischaemia–reperfusion injuries. To date, no studies have focused on the indirect cytoprotective effects of ticagrelor via adenosine receptor on the endothelium. Method: By evaluating cell viability and cleaved caspase 3 expression, we validated a model of endothelial cell apoptosis induced by hypoxia. In hypoxic endothelial cells treated with ticagrelor, we quantified the extracellular concentration of adenosine, and then we studied the involvement of adenosine pathways in the cytoprotective effect of ticagrelor. Results: Our results showed that 10 µM ticagrelor induced an anti-apoptotic effect in our model associated with an increase of extracellular adenosine concentration. Similar experiments were conducted with cangrelor but did not demonstrate an anti-apoptotic effect. We also found that A2B and A3 adenosine receptors were involved in the anti-apoptotic effect of ticagrelor in endothelial cells exposed to 2 h of hypoxia stress. Conclusion: we described an endothelial cytoprotective mechanism of ticagrelor against hypoxia stress, independent of blood elements. We highlighted a mechanism triggered mainly by the increased extracellular bioavailability of adenosine, which activates A2B and A3 receptors on the endothelium.

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Population Pharmacokinetic-Pharmacodynamic Modeling of Ropivacaine in Spinal Anesthesia

Cited by 31 publications

References 50 publications

Dexmedetomidine versus sufentanil with high‐ or low‐concentration ropivacaine for labor epidural analgesia: A randomized trial

Dexmedetomidine versus sufentanil with high‐ or low‐concentration ropivacaine for labor epidural analgesia: A randomized trial

Real Life Population Pharmacokinetics Modelling of Eight Factors VIII in Patients with Severe Haemophilia A: Is It Always Relevant to Switch to an Extended Half-Life?

Ticagrelor Prevents Endothelial Cell Apoptosis through the Adenosine Signalling Pathway in the Early Stages of Hypoxia

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