Journal of Clinical Pharmacology最新文献_第6页

Efficacy of Bile Acid Sequestrants in the Treatment of Bile Acid Diarrhea: A Meta-Analysis of Randomized Controlled Trials. 胆汁酸螯合剂治疗胆汁酸性腹泻的疗效：随机对照试验的元分析》。

IF 2.9 4区医学

Journal of Clinical Pharmacology Pub Date : 2024-10-21 DOI: 10.1002/jcph.6154

Giulia Almiron R Soares, Amanda Godoi, Patricia Marcolin, Gabriel Piredda, Estella Laia, Airton Zogaib Rodrigues

{"title":"Efficacy of Bile Acid Sequestrants in the Treatment of Bile Acid Diarrhea: A Meta-Analysis of Randomized Controlled Trials.","authors":"Giulia Almiron R Soares, Amanda Godoi, Patricia Marcolin, Gabriel Piredda, Estella Laia, Airton Zogaib Rodrigues","doi":"10.1002/jcph.6154","DOIUrl":"https://doi.org/10.1002/jcph.6154","url":null,"abstract":"Bile acid sequestrants (BASs) have often been used for bile acid diarrhea (BAD) but carry a high risk of adverse events. New generations of BASs show promising results; however, their efficacy remains unclear. This systematic review and meta-analysis was conducted using PubMed, Cochrane, and Embase to assess randomized controlled trials (RCTs) published up to November 2023 to retrieve studies that measured the parameters before and after the administration of BASs. The outcomes assessed were cessation or improvement in diarrhea, fecal consistency, abdominal cramping, frequency of diarrhea, and adverse events. Risk ratios (RRs) and mean differences with 95% confidence intervals (CIs) were pooled using a random-effects model. Statistical analyses were conducted using RStudio version 4.1.2. The protocol was prospectively registered with PROSPERO (CRD42023445444). Seven RCTs with a total of 311 patients were included, of which 168 (54%) were randomized to BASs. Among BAS-treated patients, 101 (60.1%) received colesevelam, 40 (23.8%) received chenodeoxycholate, 18 (10.7%) received cholestyramine, and 9 (5.3%) received colestid. BASs were associated with a significant improvement in the cessation of diarrhea (RR 3.27; 95% CI 2.08 to 5.15; P ≤ .05) and liquid stool to normal fecal consistency (RR 2.69; 95% CI 1.56 to 4.65; P ≤ .05), as well as an increase in abdominal cramps (RR 5.27; 95% CI 1.21 to 22.93; P ≤ .05). There were no differences in urgency, adverse events, or nausea between groups. These findings indicate that BASs are effective in the treatment of BAD, as indicated by the improvement or cessation of diarrhea episodes.","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exposure-Efficacy Analysis and Dopamine D2 Receptor Occupancy in Adults with Schizophrenia after Treatment with the Monthly Intramuscular Injectable Risperidone ISM. 每月一次肌肉注射利培酮 ISM 治疗后，成人精神分裂症患者的暴露-疗效分析和多巴胺 D2 受体占用率。

IF 2.9 4区医学

Journal of Clinical Pharmacology Pub Date : 2024-10-17 DOI: 10.1002/jcph.6152

Andreas Lindauer, Eric Snoeck, Christian Laveille, Ignacio Ayani, Lourdes Ochoa Díaz de Monasterioguren, Marcos Almendros, Javier Martínez-González, Lourdes Anta, Ibón Gutierro

{"title":"Exposure-Efficacy Analysis and Dopamine D2 Receptor Occupancy in Adults with Schizophrenia after Treatment with the Monthly Intramuscular Injectable Risperidone ISM.","authors":"Andreas Lindauer, Eric Snoeck, Christian Laveille, Ignacio Ayani, Lourdes Ochoa Díaz de Monasterioguren, Marcos Almendros, Javier Martínez-González, Lourdes Anta, Ibón Gutierro","doi":"10.1002/jcph.6152","DOIUrl":"https://doi.org/10.1002/jcph.6152","url":null,"abstract":"Dopamine D2 receptor occupancy (D2RO) significantly influences the clinical effectiveness and safety of many antipsychotic drugs. Maintaining a D2RO range of 65%-80% provides the best antipsychotic effects while minimizing adverse reactions. Data from a Phase III trial were used to establish an exposure-response relationship for monthly intramuscular Risperidone ISM (75 and 100 mg) or placebo administered to adults with schizophrenia. Pharmacodynamic analysis was based on an Emax model for Positive and Negative Syndrome Scale (PANSS) developed in NONMEM. Plasma concentrations of the active moiety were derived using a previously developed population pharmacokinetic model, which was used for D2RO simulations in conjunction with a published Emax model. The optimal D2RO range (65%-80%) was reached for the median within hours following the first injection of both Risperidone ISM doses. At steady state, median D2RO for both doses remained above 65% throughout the 28-day dosing period and demonstrated lower variability than oral risperidone. PANSS response did not differ significantly between dose groups, most likely because active moiety concentrations had already reached the plateau of the concentration-response relationship. The pharmacokinetic/pharmacodynamic analysis showed a profound placebo effect (-11.7%), and an additional maximal drug effect (-6.6%) resulting in a total PANSS improvement over time of -18.3%. Pharmacokinetic/pharmacodynamic modeling quantified a PANSS improvement over time after Risperidone ISM administration. The response was not significantly different in either dose group, likely because D2RO was already above the proposed efficacy threshold (65%) within 1 h after the first Risperidone ISM injection and remained above this level following repeated administrations.","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Population Pharmacokinetic Simulations for Dose Optimization of Tenofovir Disoproxil Fumarate in HIV-Infected Patients with Moderate-to-Severe Renal Impairment. 用于中重度肾功能损害的 HIV 感染者富马酸替诺福韦二吡呋酯剂量优化的群体药代动力学模拟。

IF 2.9 4区医学

Journal of Clinical Pharmacology Pub Date : 2024-10-17 DOI: 10.1002/jcph.6153

Apinya Boonpeng, Noppaket Singkham, Chanadda Wutthikul, Thanawan Rattanakul, Pinmanee Weeket, Chananan Saengpraphanan, Rungrawin Plaengnok

{"title":"Population Pharmacokinetic Simulations for Dose Optimization of Tenofovir Disoproxil Fumarate in HIV-Infected Patients with Moderate-to-Severe Renal Impairment.","authors":"Apinya Boonpeng, Noppaket Singkham, Chanadda Wutthikul, Thanawan Rattanakul, Pinmanee Weeket, Chananan Saengpraphanan, Rungrawin Plaengnok","doi":"10.1002/jcph.6153","DOIUrl":"https://doi.org/10.1002/jcph.6153","url":null,"abstract":"Tenofovir disoproxil fumarate (TDF) requires dosage adjustments from the standard 300 mg once daily to every 48-96 h for moderate-to-severe renal impairment to avoid excessive exposure. However, this extended interval can lead to variable drug exposure and inconvenience. This study aimed to utilize the population pharmacokinetic (PPK) models to optimize TDF dosing regimens for HIV-infected patients with renal impairment. A systematic literature search was conducted across PubMed, Cochrane Library, and Scopus databases to identify relevant PPK studies of TDF in HIV-infected patients. From the included studies, the PPK models and associated parameters were extracted. Monte Carlo simulations (n = 2000) were performed to generate concentration-time profiles and derive PK parameters compared against reference ranges. For moderate renal impairment, the TDF 150 mg once-daily regimen achieved cumulative exposure comparable to the approved 300 mg every-other-day regimen. In severe renal impairment, TDF 75-100 mg administered once daily provided similar cumulative exposure as 300 mg every 72-96 h regimen while maintaining daily exposure comparable to the standard dose in patients with normal renal function. The approved extended dosing intervals of 72-96 h exhibited high drug exposure variability, initially resulting in supratherapeutic levels followed by suboptimal levels preceding the subsequent dose administration. In conclusion, administering smaller once-daily doses of TDF maintains consistent daily drug exposure comparable to the standard dose in patients with normal renal function while reducing variability in drug exposure, potentially mitigating the risk of nephrotoxicity. However, additional clinical studies are required to confirm these findings.","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Efficacy and Safety of SGLT-2 Inhibitors in Acute Myocardial Infarction: A Systematic Review and Meta-Analysis. SGLT-2 抑制剂在急性心肌梗死中的疗效和安全性：系统回顾与元分析》。

IF 2.9 4区医学

Journal of Clinical Pharmacology Pub Date : 2024-10-17 DOI: 10.1002/jcph.6149

Hila Asham, Samad Ghaffari, Mohammadreza Taban-Sadeghi, Taher Entezari-Maleki

{"title":"Efficacy and Safety of SGLT-2 Inhibitors in Acute Myocardial Infarction: A Systematic Review and Meta-Analysis.","authors":"Hila Asham, Samad Ghaffari, Mohammadreza Taban-Sadeghi, Taher Entezari-Maleki","doi":"10.1002/jcph.6149","DOIUrl":"https://doi.org/10.1002/jcph.6149","url":null,"abstract":"Since there is no specific recommendation of sodium-glucose cotransporter-2 (SGLT-2) inhibitors in acute myocardial infarction (MI), this systematic review and meta-analysis was performed to address this lack of evidence. Scopus, Embase, PubMed, Web of Sciences, and Cochrane Library were searched from inception until May 30, 2024. We used both random and fixed-effects models for data analyses. Odds ratio (OR) and standard means difference (SMD) were performed for binary and continuous variables, respectively. Nine studies including five randomized clinical trials (RCTs) and four observational studies including 15,595 individuals with acute MI were entered. Overall, SGLT-2 inhibitors are significantly associated with a reduction of hospitalization for heart failure (OR, 0.78; 95% CI, 0.63 to 0.97; P = .02; I2 = 0%) and all-cause mortality (OR, 0.55; 95% CI, 0.38 to 0.81; P = .002; I2 = 0%) based on the RCTs and observational studies, respectively. SGLT-2 inhibitors also significantly improved the left ventricular ejection fraction (SMD, 0.36; 95% CI, 0.02 to 0.70; P = .04; I2 = 62%) among RCTs. Further evaluation of these drugs also revealed an acceptable safety profile without any major adverse events. In conclusion, although SGLT-2 inhibitors may have some clinical benefits among acute MI individuals, further RCTs are still needed to provide robust evidence regarding the use of SGLT-2 inhibitors in this setting.","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pharmacological Management of Sleep-Wake Disturbances in Delirium. 谵妄患者睡眠-觉醒紊乱的药物治疗。

IF 2.9 4区医学

Journal of Clinical Pharmacology Pub Date : 2024-10-16 DOI: 10.1002/jcph.6151

Erik A Levinsohn, Varsha Radhakrishnan, Haley Euting, Gary B Kaplan

{"title":"Pharmacological Management of Sleep-Wake Disturbances in Delirium.","authors":"Erik A Levinsohn, Varsha Radhakrishnan, Haley Euting, Gary B Kaplan","doi":"10.1002/jcph.6151","DOIUrl":"https://doi.org/10.1002/jcph.6151","url":null,"abstract":"Delirium is a heterogeneous syndrome primarily characterized by fluctuations in attention and awareness. Sleep-wake disturbances are a common and significant feature of delirium and can manifest as circadian rhythm inversion, sleep fragmentation, and reduced rapid eye movement (REM) and slow-wave sleep. Some literature suggests that the relationship between sleep disruption and delirium is reciprocal wherein the two reinforce one another and may share an underlying etiology. As there are no FDA-approved medications for delirium or delirium-related sleep disturbances, management is primarily focused on addressing underlying medical concerns and promoting physiologic circadian patterns with non-pharmacological behavioral interventions. In practice, however, medications are often used, albeit with limited evidence to support their use. This literature review explores the pharmacology and pharmacokinetics of several medications with literature investigating their use in delirium: melatonin, ramelteon, dual orexin receptor antagonists (DORAs), and dexmedetomidine. Current evidence suggests a possible benefit of ramelteon or melatonin, dexmedetomidine for patients in the ICU setting, and DORAs as therapeutic options for the re-regulation of sleep-wake cycle disruption in delirium. We discuss pertinent pharmacokinetic and pharmacodynamic factors that may influence clinical decision-making regarding these interventions.","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pharmacokinetics and Safety of a Novel Extended-Release Microsphere Formulation of Risperidone in Patients with Schizophrenia or Schizoaffective Disorder. 新型利培酮缓释微球制剂在精神分裂症或情感分裂症患者中的药代动力学和安全性。

IF 2.9 4区医学

Journal of Clinical Pharmacology Pub Date : 2024-10-15 DOI: 10.1002/jcph.6143

David P Walling, Ying Dong, Robert Litman, Wenyan Wang, Chunli Liu, Joe Tai, Pinglan Liu, Yanan Shi, Wanhui Liu, Fenghua Fu, Kaoxiang Sun

{"title":"Pharmacokinetics and Safety of a Novel Extended-Release Microsphere Formulation of Risperidone in Patients with Schizophrenia or Schizoaffective Disorder.","authors":"David P Walling, Ying Dong, Robert Litman, Wenyan Wang, Chunli Liu, Joe Tai, Pinglan Liu, Yanan Shi, Wanhui Liu, Fenghua Fu, Kaoxiang Sun","doi":"10.1002/jcph.6143","DOIUrl":"https://doi.org/10.1002/jcph.6143","url":null,"abstract":"Risperidone extended-release injectable suspension (R-ERIS; marketed as RYKINDO) is a novel immediate-release version of risperidone formulated as extended-release microspheres for biweekly intramuscular injection to treat schizophrenia in adults. The pharmacokinetics (PK) and safety of R-ERIS were evaluated in a multicenter, randomized, open-label, multiple-dose study in patients with stable schizophrenia or schizoaffective disorder. Eligible patients (N = 108) 18 to 65 years old were randomized (1:1) to receive IM injections of R-ERIS 25 mg or the comparator, a biweekly risperidone long-acting injectable (BW-RLAI; marketed as RISPERDAL CONSTA) 25 mg for a total of 5 injections. The primary objective was to evaluate the relative bioavailability of active moiety (risperidone plus 9-hydroxyrisperidone) at steady state. Blood samples were analyzed for risperidone and 9-hydroxyrisperidone using a validated, specific, and sensitive liquid chromatography with tandem mass spectrometry method. Plasma concentration-time data were analyzed using non-compartmental methods. Pharmacokinetic parameters were calculated based on individual patient PK profiles. Safety was assessed using standard measures. At steady state, mean plasma concentrations of the active moiety were similar for R-ERIS and BW-RLAI. R-ERIS rapidly released risperidone after the injection without apparent lag time. Plasma active moiety levels reached steady state after the second injection of R-ERIS. The elimination of the drug was completed approximately 2 weeks earlier for R-ERIS as compared to that for BW-RLAI. R-ERIS was safe and well tolerated. Overall, R-ERIS exhibited a faster onset and offset than BW-RLAI and statistical analysis of exposure parameters demonstrated bioequivalence at steady state.","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exploring the Impact of Developmental Clearance Saturation on Propylene Glycol Exposure in Adults and Term Neonates Using Physiologically Based Pharmacokinetic Modeling. 利用基于生理学的药代动力学模型探索发育清除饱和对成人和足月新生儿丙二醇暴露的影响。

IF 2.9 4区医学

Journal of Clinical Pharmacology Pub Date : 2024-10-15 DOI: 10.1002/jcph.6150

Olusola Olafuyi, Robin Michelet, Michael Garle, Karel Allegaert

{"title":"Exploring the Impact of Developmental Clearance Saturation on Propylene Glycol Exposure in Adults and Term Neonates Using Physiologically Based Pharmacokinetic Modeling.","authors":"Olusola Olafuyi, Robin Michelet, Michael Garle, Karel Allegaert","doi":"10.1002/jcph.6150","DOIUrl":"https://doi.org/10.1002/jcph.6150","url":null,"abstract":"Propylene glycol (PG) is a pharmaceutical excipient which is generally regarded as safe (GRAS), though clinical toxicity has been reported. PG toxicity has been attributed to accumulation due to saturation of the alcohol dehydrogenase (ADH)-mediated clearance pathway. This study aims to explore the impact of the saturation of ADH-mediated PG metabolism on its developmental clearance in adults and neonates and assess the impact of a range of doses on PG clearance saturation and toxicity. Physiologically based pharmacokinetic (PBPK) models for PG in adults and term neonates were developed using maximum velocity (Vmax) and Michaelis-Menten's constant (Km) of ADH-mediated metabolism determined in vitro in human liver cytosol, published physicochemical, drug-related and ADH ontogeny parameters. The models were validated and used to determine the impact of dosing regimen on PG clearance saturation and toxicity in adults and neonates. The Vmax and Km of PG in human liver cytosol were 1.57 nmol/min/mg protein and 25.1 mM, respectively. The PG PBPK model adequately described PG PK profiles in adults and neonates. The PG dosing regimens associated with saturation and toxicity were dependent on both dose amount and cumulative in standard dosing frequencies. Doses resulting in saturation were higher than those associated with clinically observed toxicity. In individuals without impaired clearance or when PG exposure is through formulations that contain excipients with possible interaction with PG, a total daily dose of 100-200 mg/kg/day in adults and 25-50 mg/kg/day in neonates is unlikely to result in toxic PG levels or PG clearance saturation.","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Inflammation Decreases Ciclosporin Metabolism in Allogeneic Hematopoietic Stem Cell Transplantation Recipients. 炎症会降低同种异体造血干细胞移植受者体内的环孢素代谢。

IF 2.9 4区医学

Journal of Clinical Pharmacology Pub Date : 2024-10-09 DOI: 10.1002/jcph.6141

David Malnoë, Mathilde Bories, Morgane Pierre-Jean, Tony Marchand, Pascal Le Corre

{"title":"Inflammation Decreases Ciclosporin Metabolism in Allogeneic Hematopoietic Stem Cell Transplantation Recipients.","authors":"David Malnoë, Mathilde Bories, Morgane Pierre-Jean, Tony Marchand, Pascal Le Corre","doi":"10.1002/jcph.6141","DOIUrl":"10.1002/jcph.6141","url":null,"abstract":"Graft-versus-host disease (GVHd) remains a significant challenge following allogeneic hematopoietic stem cell transplantation (HSCT). Prevention of GVHd relies mainly on the use of calcineurin inhibitors, notably ciclosporin that exhibits complex pharmacokinetics influenced by many factors including drug-drug interactions (DDIs). Due to the downregulation of drug metabolizing enzymes and transporters, it has been postulated that inflammation may be a contributing factor to the variability observed in ciclosporin pharmacokinetics. This study aimed to assess the impact of inflammation, as indicated by C-reactive protein (CRP) levels, on the metabolism of ciclosporin in adult allogeneic HSCT recipients. A retrospective observational study was conducted at Rennes University Hospital involving 71 adult HSCT patients. The relationship between the intensity of inflammation (no-to-mild, moderate, and severe), and the metabolism of ciclosporin (estimated by the concentration/dose ratio) was assessed. Severe inflammation significantly decreased the metabolism of ciclosporin, as evidenced by higher concentration/dose ratios. Thanks to the daily dose adjustment, inflammation did not influence the blood levels of ciclosporin. Interestingly, DDIs did not emerge as a significant covariate in influencing ciclosporin metabolism. This is likely because the CYP3A4 inhibitory potential of interacting drugs may be masked in HSCT patients where metabolism is already upstream downregulated by inflammation. The study highlights the intricate relationship between inflammation and ciclosporin pharmacokinetics in HSCT patients. This underscores the necessity for therapeutic monitoring and the potential adjustment of dosage strategies based on the inflammatory status. These insights could contribute to the development of more personalized, optimized, and effective management strategies for HSCT recipients.","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142394477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dried Blood Spots Sampling and Population Pharmacokinetic Modeling for Dosing Optimization of Piperacillin in Chinese Neonates. 干血斑采样和群体药代动力学模型用于优化中国新生儿哌拉西林的用药剂量

IF 2.9 4区医学

Journal of Clinical Pharmacology Pub Date : 2024-10-07 DOI: 10.1002/jcph.6145

Pei Li, Quanyao Chen, Yao Chen, Zhi Zheng, Xiaoyan Zhao, Huayan Chen, Qian Liu, Feifan Xie

{"title":"Dried Blood Spots Sampling and Population Pharmacokinetic Modeling for Dosing Optimization of Piperacillin in Chinese Neonates.","authors":"Pei Li, Quanyao Chen, Yao Chen, Zhi Zheng, Xiaoyan Zhao, Huayan Chen, Qian Liu, Feifan Xie","doi":"10.1002/jcph.6145","DOIUrl":"https://doi.org/10.1002/jcph.6145","url":null,"abstract":"Piperacillin is commonly used off-label in neonates for the treatment of bacterial infections. This study aimed to assess a dried blood spots (DBS)-based microsampling strategy for supporting population pharmacokinetics and treatment optimization of piperacillin in Chinese neonates. DBS samples from neonatal patients were collected at predefined intervals. Drug blood concentrations were quantified using a validated ultra-high-performance liquid chromatography-tandem mass spectrometry method. A population pharmacokinetic model was developed using a nonlinear mixed-effects modeling approach. The pharmacokinetic/pharmacodynamics (PK/PD) target was 75% of the time with the unbound drug plasma concentration above the minimum inhibitory concentration (fT>MIC), with a toxicity threshold of unbound drug plasma trough concentration above 64 mg/L. A total of 45 piperacillin samples from 24 neonates were collected. The pharmacokinetics of piperacillin was described using a one-compartment model with postmenstrual age (PMA) as the most significant covariate on clearance. Simulations showed that dosing regimens achieving >90% PK/PD target attainment with <10% risk of possible toxicity were: PMA 33-35 weeks (50 mg/kg q12h), 35-37 weeks (50 mg/kg q8h), and 37-41 weeks (50 mg/kg q6h). In conclusion, Using DBS sampling, we developed a population pharmacokinetic model of piperacillin in Chinese neonates, incorporating PMA to determine optimal dosing regimens.","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142394476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Addressing Drug-Drug Interaction Knowledge Gaps at the Time of Approval: An Analysis of FDA Postmarketing Requirements and Commitments from 2009 to 2023. 在批准时解决药物相互作用知识差距：美国食品和药物管理局 2009 年至 2023 年上市后要求和承诺分析》（Analysis of FDA Postmarketing Requirements and Commitments from 2009 to 2023）。

IF 2.9 4区医学

Journal of Clinical Pharmacology Pub Date : 2024-10-03 DOI: 10.1002/jcph.6142

Sarah Ridge, Xinning Yang, Rajanikanth Madabushi, Anuradha Ramamoorthy

{"title":"Addressing Drug-Drug Interaction Knowledge Gaps at the Time of Approval: An Analysis of FDA Postmarketing Requirements and Commitments from 2009 to 2023.","authors":"Sarah Ridge, Xinning Yang, Rajanikanth Madabushi, Anuradha Ramamoorthy","doi":"10.1002/jcph.6142","DOIUrl":"https://doi.org/10.1002/jcph.6142","url":null,"abstract":"It has become increasingly common for patients to rely on the use of multiple prescription medications. The management of polypharmacy requires careful consideration for how drugs are metabolized and their potential for interaction with other drugs. Drug-drug interaction (DDI) assessments are typically performed in a stepwise manner during drug development, though knowledge gaps can exist at the time of approval. The US Food and Drug Administration can establish postmarketing requirements (PMRs) or postmarketing commitments (PMCs) to address these knowledge gaps. In this study, we systematically evaluated PMRs and PMCs established to new molecular entities (NMEs) at the time of initial approval between 2009 and 2023, for the assessment of pharmacokinetics-based DDIs (i.e., drug metabolizing enzyme- and transporter-related DDIs). We found that 22% of NMEs had at least one DDI-related PMR or PMC, with a total of 263 that were pharmacokinetic based. Of these, 67% were for the assessment of drug metabolizing enzymes, which were established most frequently for their evaluation as a substrate, and 28% for transporters, which were established most frequently for their evaluation as an inhibitor. The 89% of PMRs and PMCs that were considered fulfilled had a revision to the United States prescribing information, the majority of which resulted in updated new instructions for use. This study highlights the value in conducting PMRs and PMCs early in the drug development process allowing broad patient inclusion at the time of initial drug approval.","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142373315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0