Association of obesity with ropivacaine and sufentanil EC50 in labor analgesia: a single-center prospective studyLiu, Zunyi; Zhou, Xuelan; Zhu, Jiang
2025 European Journal of Clinical Pharmacology
doi: 10.1007/s00228-024-03800-8pmid: 39774874
ObjectiveIn part I, measure the EC50 of sufentanil in obese and non-obese parturients combined with 0.1% ropivacaine and compare the differences. Similarly, in part II, measure the EC50 of ropivacaine in obese and non-obese parturients combined with 0.5 µg/ml sufentanil and compare the differences.MethodsThis study comprises two parts, with an initial intention to enroll 120 full-term primiparous women who underwent vaginal delivery and sought epidural analgesia. Each part includes an obese group (OA group, Obese Adults, defined as prepartum BMI≥29 kg/m2) and a non-obese group (CON group, Control group, defined as 18.5<prepartum BMI<28 kg/m2), with 30 participants in each. Both parts, for both obese and non-obese women, utilized an initial concentration of 0.1% ropivacaine with 0.5 µg /ml sufentanil. The initial concentration of sufentanil is 0.5 µg/ml. When the NRS score is ≤3 within 30min after analgesia, it is considered effective analgesia, and the concentration of sufentanil in the next parturients decreases by 0.05 µg/ml. Otherwise, the concentration of sufentanil in the next parturient will increase by 0.05 µg/ml. The second part uses the same method to measure the EC50 of ropivacaine (increase or decrease by 0.01%) in the OA group and CON group combined with 0.5 µg/ml sufentanil, with 30 participants in each group. EC50 measurements were performed through up-and-down sequential allocation, with effective analgesia defined as an NRS score ≤3, 30 min post-analgesia.ResultsIn part I, the EC50 of epidural sufentanil in the OA group was 0.090 µg/ml (95% CI, 0.061~0.115µg/ml), and in the CON group, it was 0.170µg/ml (95% CI, 0.117~0.219µg/ml). In part II, the EC50 of epidural ropivacaine in the OA group was 0.048% (95% CI, 0.041~0.053%), and in the CON group, it was 0.070% (95% CI, 0.064~0.075%). The secondary outcomes in both parts of the study showed no statistically significant differences.ConclusionObese parturients exhibited significantly lower EC50 values for ropivacaine and sufentanil compared to non-obese parturients. Lower concentrations of both agents can be considered for labor analgesia in obese parturients.
Features and results availability of non-commercial Spanish COVID-19 trials: a systematic review of clinical trial registers and corresponding literatureDal-Ré, Rafael; García-Méndez, Elena; Mahillo-Fernández, Ignacio
2025 European Journal of Clinical Pharmacology
doi: 10.1007/s00228-024-03791-6pmid: 39789343
ObjectivesThis study aimed to characterize non-commercial Spanish COVID-19 trials and to determine the availability of results. Differences in outcomes according to the interventions assessed (medicines, non-medicines) will also be determined.MethodsThis systematic review was conducted in March 2024 by searching non-commercial Spanish COVID-19 trials on four registers (EUCTR, Clinical.Trials.gov, ISRCTN, DRKS) and the WHO ICTRP. Phase-1 medicines trials were excluded. Several variables were retrieved from registers. Publication of main trial results were searched on PubMed, Cochrane COVID-19 Study Register, and Google Scholar. Journals’ impact factor and articles’ citations on Google Scholar were also registered. Results from medicines and non-medicines trials extracted from registers and articles were compared.ResultsA total of 170 trials (57.1% medicines trials) were identified. These 170 trials were randomized (87.1%), masked (41.8%), or multicenter (39.4%); a total of 15,555 participants were enrolled, mostly in small trials (median, n = 88). Only 8.8% (15/170) of trials posted results on the registers; only 47.6% (81/170) of trials had either published results or posted them on registers. Publications accounted for 92.6% (75/81) of these. Articles were published in 56 different journals, had a median impact factor of 4.4 and a median of 10 citations. Most (58.7%, 44/75) described negative results. There were statistically significant differences (p < 0.001) between medicines and non-medicines trials on timely registration and on being multicenter. This was also the case among published trials with respect to negative results of the primary endpoint.ConclusionAlthough most trials were randomized, a minority were multicenter, large, or masked. Trial results should be posted on the registers to make them accessible to everyone.
Correlation of cyclosporine A blood concentration with kidney injury for pediatric patients after hematopoietic stem cell transplantation: a retrospective cohort studyShi, Wei; Qiu, Xin; Huang, Liang; Zeng, Linan; Lu, Runxin; Li, Hailong; Zou, Kun; Jia, Zhijun; Cheng, Guo; Yu, Qin; Zhao, Limei; Zhang, Lingli
2025 European Journal of Clinical Pharmacology
doi: 10.1007/s00228-024-03792-5pmid: 39775018
BackgroundThe potential nephrotoxicity of cyclosporine A (CsA) has been a problem for treating graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the relationship between CsA blood concentration and acute kidney injury (AKI) in pediatric patients after allo-HSCT remains unclear.MethodsWe performed a retrospective study including pediatric patients who received allo-HSCT in West China Second Hospital of Sichuan University from 2000 to 2022 and collected their clinical data. Included patients’ CsA blood concentration were divided into three cohorts according to the guideline. Multivariate logistic regression was used to estimate the relationship between AKI and CsA blood concentration and other factors. And the maximum cut-off value for the safe blood concentration range of CsA was obtained by the receiver operating characteristic (ROC) curve.ResultsSeventy-nine patients (average age 6.75 ± 4.25) were included. The incidence of kidney injury for three CsA blood concentration cohorts (< 200 ng/ml, 200–300 ng/ml, > 300 ng/ml) were 21.30%, 23.50%, and 66.70%, respectively. A multivariate logistic regression identified CsA blood concentration (> 300 ng/ml) and infection were risk factors for AKI (OR <200 ng/ml: 0.115, 95% CI: 0.029–0.458; OR 200–300 ng/ml: 0.184, 95% CI: 0.036–0.929; OR infection: 5.006, 95% CI: 1.491–16.810). Meanwhile, the maximum cut-off value for the safe blood concentration range of CsA is 276.85 ng/ml with an AUC value of 0.684 (P = 0.010).ConclusionIn conclusion, clinical treatment for the pediatric patients after allo-HSCT may be considered to control the blood concentration of CsA in 200–276.85 ng/ml and closely monitoring patients who have infections.
Population pharmacokinetics of bedaquiline: a systematic reviewJin, Jie; Cao, Jie; Zhang, Ruoying; Zheng, Lifang; Cai, Xinjun; Li, Jinmeng
2025 European Journal of Clinical Pharmacology
doi: 10.1007/s00228-024-03788-1pmid: 39779577
Background and objectivesBedaquiline (BDQ) plays a critical role in the treatment of multidrug-resistant tuberculosis (MDR-TB). However, the large pharmacokinetic (PK) variability of BDQ presents a significant challenge in its clinical use. This study aimed to summarize the population PK characteristics of BDQ and to identify significant covariates affecting the PK variation of BDQ.MethodsThe PubMed and Web of Science databases were systematically searched from their inception to October 1, 2023. Population pharmacokinetics (PPK) studies on BDQ were searched and identified in this review. The PK characteristics of included studies and the significant covariates were systematically summarized.ResultsEight studies conducted in adults and one in children and adolescents were included in this review. A three disposition compartments with dynamic absorption transport chamber model was the commonly used structural model for BDQ. Body weight, race, albumin, and concomitant medication were significant covariates affecting BDQ PK variation. With the increase of weight and albumin levels, the clearance (CL) of BDQ was gradually increased. The average CL value per body weight in children was 1.49-fold higher than that in adults. Black race patients had an 84% higher CL than other populations. Moreover, combined with rifampicin and rifapentine, BDQ had 378% and 296% higher clearance rates, respectively.ConclusionsBody weight, race, albumin level, and concomitant medication may be important factors affecting patients’ exposure differences. Further PPK studies of BDQ are needed to facilitate optimal dosing regimens.
Pharmacogenetics of opioid medications for relief of labor pain and post-cesarean pain: a systematic review and meta-analysisGiacon, Martina; Cargnin, Sarah; Talmon, Maria; Terrazzino, Salvatore
2025 European Journal of Clinical Pharmacology
doi: 10.1007/s00228-024-03798-zpmid: 39774699
ObjectiveSeveral studies have attempted to identify genetic determinants of clinical response to opioids administered during labor or after cesarean section. However, their results were often contrasting. A systematic review and meta-analysis was conducted to quantitatively assess the association between gene polymorphisms and clinical outcomes of opioid administration in the treatment of labor pain and post-cesarean pain.MethodsA comprehensive search was performed up to December 2023 using PubMed, Web of Knowledge, Cochrane Library, and OpenGrey databases. The clinical endpoints of interest were pain score after opioid treatment, total opioid consumption, patient’s analgesic satisfaction, and incidence of opioid side effects. Random-effects meta-analyses were conducted when data were available in at least three studies.ResultsTwenty-six studies enrolling 7765 patients were included in the systematic review. Overall, a total of 12 candidate polymorphic genes (OPRM1, COMT, CYP2D6, CYP3A4, ABCB1, ABCC3, UGT2B7, CGRP, OPRK1, OPRD1, KCNJ6, KCNJ9) were considered by the included studies, among which the most investigated variant was OPRM1 rs1799971. Overall pooled results indicated that individuals carrying the G allele of OPRM1 rs1799971 required higher opioid doses for pain management in comparison to rs1799971 AA subjects (standardized mean difference: 0.26; 95% CI: 0.09–0.44; P = 0.003). Such an association was confirmed in the subgroups of patients with labor pain and post-cesarean pain.ConclusionThe present meta-analysis provides strong evidence of an association between OPRM1 rs1799971 and opioid dose requirement for relief of labor pain or post-cesarean pain. However, given the insufficient evidence for other polymorphic gene variants, large studies are still needed to investigate the impact of genetic variability on the efficacy and safety of opioid medications for relief of labor pain and post-cesarean pain (INPLASY Registration No. 202410040).