Pharmacotherapy最新文献

{"title":"A systematic review of clozapine-associated inflammation and related monitoring.","authors":"Jonathan G Leung, Lusi Zhang, Matej Markota, Vicki L Ellingrod, Danielle J Gerberi, Jeffrey R Bishop","doi":"10.1002/phar.2887","DOIUrl":"10.1002/phar.2887","url":null,"abstract":"<p><p>Clozapine is an effective antipsychotic medication used for treatment-resistant schizophrenia. However, it is underutilized due to rigorous hematologic monitoring requirements and many adverse drug reactions. Publications have highlighted the occurrence of inflammatory reactions, some life-threatening, particularly during the early stages of clozapine treatment. Although guidelines have suggested monitoring for inflammatory processes during clozapine initiation, screening in clinical practice is not universal. This systematic review aimed to investigate the relationship between clozapine and inflammation and assess the importance of monitoring for inflammatory reactions. A comprehensive literature search yielded 6915 unique publication records after removal of duplicates. After a rigorous screening process, 75 publications were included in the review, which focused on three main aspects: (i) the impact of clozapine on inflammatory markers, (ii) monitoring cardiac and other organ function during clozapine-associated inflammatory processes, and (iii) monitoring non-specific signs and symptoms of inflammation. Elevated levels of C-reactive protein (CRP) and several proinflammatory cytokines have been observed in association with clozapine treatment. However, the practicality of measuring specific markers in clinical practice remains uncertain. Current evidence supports monitoring CRP levels during the first 4-8 weeks of treatment, especially to facilitate myocarditis screening. Further research is needed to establish clinically relevant CRP thresholds for intervention. The implementation of monitoring protocols during the early phase of clozapine treatment may mitigate adverse reactions and allow for continued use of clozapine. Future studies should also explore the association between clozapine-associated inflammation and pneumonia, as well as investigate the impact of inflammation on clozapine metabolism to predict the need for dose adjustment. These endeavors may facilitate the development and implementation of evidence-based guidelines for the monitoring of clozapine-associated inflammation.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41237525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of a modified MINDS-based protocol for management of alcohol withdrawal syndrome on an inpatient medical service.","authors":"Kevin M Krcmarik, Benjamin J Hulley, Jiayi Huang, Derek Juang, Peter Cadman, Charisma Urbiztondo, Christine Vo, Jaclyn Vargas, Ramin Motarjemi, Tarlan Moinizandi, Brian Kwan","doi":"10.1002/phar.2855","DOIUrl":"10.1002/phar.2855","url":null,"abstract":"<p><strong>Objective: </strong>To determine if a novel symptom-based alcohol withdrawal syndrome (AWS) protocol in a US Veterans cohort leads to significant clinical improvements in patient outcomes and safety.</p><p><strong>Background: </strong>Prior studies of AWS management, oftentimes using the revised version of the Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) index, have demonstrated the effectiveness of symptom-triggered therapy for AWS. The Minnesota Detoxification Scale (MINDS) is an alternative to the CIWA-Ar index but remains unevaluated outside of the intensive care unit (ICU) setting. This study assesses outcomes in AWS management prior to and after the implementation of a novel MINDS-based AWS protocol (SDAWP) utilizing a revised MINDS index (MINDS-rev) in an inpatient medical ward setting.</p><p><strong>Methods: </strong>Retrospective cohort study including encounters prior to (n = 342) and after (n = 338) the implementation of the protocol. Pre- and post-protocol encounters were selected by combinations of diagnostic codes and charting elements. Outcome measures of AWS management were obtained in both groups. The primary endpoint was median total benzodiazepine exposure. Secondary outcomes included median length of hospitalization, median duration of benzodiazepine administration, and the incidence of complications.</p><p><strong>Results: </strong>The median total benzodiazepine exposure in the post-SDAWP group was significantly lower than the pre-SDAWP group (21.2 vs. 12.0 mg, p < 0.0001) and for a significantly shorter median duration of time (4.0 vs. 3.0 days, p < 0.0001). There was no significant difference in the median length of stay (4.0 vs. 4.0 days, p = 0.50). The incidence of delirium tremens (21 vs. 7, p = 0.01) and need for transfer to a higher level of care (33 vs. 12, p = 0.002) was significantly lower in the post-SDAWP group.</p><p><strong>Conclusion: </strong>The SDAWP has provided significant improvements in AWS management in our institution and may potentially serve as a template for wider use in other inpatient settings.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10025299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using population pharmacokinetics to optimize initial vancomycin dosing guidelines for neonates to treat sepsis caused by coagulase-negative staphylococcus.","authors":"Erin Chung, Winnie Seto","doi":"10.1002/phar.2865","DOIUrl":"10.1002/phar.2865","url":null,"abstract":"<p><strong>Introduction: </strong>Vancomycin dosing tailored for newborns is challenging due to the significant influence of maturation and organ function on pharmacokinetics. Population pharmacokinetic (popPK) models can be used to improve target attainment in neonates.</p><p><strong>Objectives: </strong>The primary objective was to derive and evaluate a popPK model of intravenous vancomycin for neonates. Second, the predictive performance of this popPK model was compared with published popPK models.</p><p><strong>Methods: </strong>This is a retrospective cohort study of neonates admitted to the neonatal intensive care unit receiving intravenous vancomycin. A popPK model was derived with 70% of the dataset using a nonlinear mixed effects modeling method. The predictive performance of the current popPK model was validated and compared with 22 published popPK models using the remaining 30% of the dataset. Monte Carlo simulations (MCS) were performed to derive optimal dosing regimens to treat neonatal sepsis caused by coagulase-negative staphylococci (CoNS).</p><p><strong>Results: </strong>Among 655 vancomycin courses from 448 neonates, 78% of vancomycin trough concentrations were outside target range (10-15 mg/L) for central nervous system infections and 43% were outside target range (5-12 mg/L) for other infections using the institution's vancomycin dosing. A one-compartment model best described the observed data with a mean clearance of 0.11 ± 0.03 L/kg/h and volume of distribution (V) of 1.02 ± 0.08 L/kg. Body weight (WT), postmenstrual age (PMA), and serum creatinine (SCr) were significant covariates associated with clearance (p < 0.001) and body WT was a significant covariate associated with V (p = 0.009). Our study's popPK model has similar or better accuracy and precision than other published models. MCS-derived vancomycin doses from the validated model achieved >90% target attainment for a steady state through target range of 10-15 mg/L in the majority of PMA and SCr categories (78%) to treat CoNS sepsis.</p><p><strong>Conclusion: </strong>A vancomycin dosing guideline derived from a validated popPK model in neonates with CoNS sepsis is recommended to improve target attainment.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10082469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CYP2D6-guided opioid therapy for adults with cancer pain: A randomized implementation clinical trial.","authors":"Scott A Mosley, Emily Cicali, Alex Del Cueto, Diane G Portman, Kristine A Donovan, Yan Gong, Taimour Langaee, Priya Gopalan, Jessica Schmit, Jason S Starr, Natalie Silver, Young D Chang, Sahana Rajasekhara, Joshua E Smith, Heloisa P Soares, Michael Clare-Salzler, Petr Starostik, Thomas J George, Howard L McLeod, Roger B Fillingim, J Kevin Hicks, Larisa H Cavallari","doi":"10.1002/phar.2875","DOIUrl":"10.1002/phar.2875","url":null,"abstract":"<p><strong>Introduction: </strong>The CYP2D6 enzyme metabolizes opioids commonly prescribed for cancer-related pain, and CYP2D6 polymorphisms may contribute to variability in opioid response. We evaluated the feasibility of implementing CYP2D6-guided opioid prescribing for patients with cancer and reported pilot outcome data.</p><p><strong>Methods: </strong>Adult patients from two cancer centers were prospectively enrolled into a hybrid implementation-effectiveness clinical trial and randomized to CYP2D6-genotype-guided opioid selection, with clinical recommendations, or usual care. Implementation metrics, including provider response, medication changes consistent with recommendations, and patient-reported pain and symptom scores at baseline and up to 8 weeks, were assessed.</p><p><strong>Results: </strong>Most (87/114, 76%) patients approached for the study agreed to participate. Of 85 patients randomized, 71% were prescribed oxycodone at baseline. The median (range) time to receive CYP2D6 test results was 10 (3-37) days; 24% of patients had physicians acknowledge genotype results in a clinic note. Among patients with CYP2D6-genotype-guided recommendations to change therapy (n = 11), 18% had a change congruent with recommendations. Among patients who completed baseline and follow-up questionnaires (n = 48), there was no difference in change in mean composite pain score (-1.01 ± 2.1 vs. -0.41 ± 2.5; p = 0.19) or symptom severity at last follow-up (3.96 ± 2.18 vs. 3.47 ± 1.78; p = 0.63) between the usual care arm (n = 26) and genotype-guided arm (n = 22), respectively.</p><p><strong>Conclusion: </strong>Our study revealed high acceptance of pharmacogenetic testing as part of a clinical trial among patients with cancer pain. However, provider response to genotype-guided recommendations was low, impacting assessment of pain-related outcomes. Addressing barriers to utility of pharmacogenetics results and clinical recommendations will be critical for implementation success.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10840965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10214439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anticoagulant drug-drug interactions with cannabinoids: A systematic review.","authors":"Maureen A Smythe, Wendy Wu, Candice L Garwood","doi":"10.1002/phar.2881","DOIUrl":"10.1002/phar.2881","url":null,"abstract":"<p><p>This systematic review evaluates the extent to which the effect of anticoagulants may be altered in the presence of cannabinoids. The following databases were searched: EMBASE, PubMed, Web of Science, Scopus, PscycINFO, and CINAHL from database inception through May 2023. Search terms included cannabis AND anticoagulant AND drug interactions and related keywords. The major outcome was hemorrhage or thrombosis and if available the relative change in quantitative intensity of anticoagulation after cannabinoid exposure. The search generated 959 citations. After the removal of 440 duplicates, 519 citations were screened. Overall, with the exception of warfarin, evidence supporting an interaction between cannabinoids and anticoagulants is non-existent. Seven case reports evaluating an interaction with warfarin were reported. Cannabis doses involved were either extremely high (e.g., >260 mg/day of delta-9-tetrahydrocannabidiol [THC] or >600 mg/day of cannabidiol [CBD]) or were not known. Hemorrhage was identified in 14.2% (1/7) of reports and thrombosis in 0%. Quantitative anticoagulation levels were increased in patients on warfarin (elevated International Normalized Ratio [INR]) in six of seven cases. A maximum INR change was available in five of seven reports, ranging from +0.4 to +9.61. One report found no change in INR after 4 days of medical cannabis exposure. Another report outlined two separate episodes of INR elevation associated with bleeding requiring hospitalization and reversal after marijuana smoking. Four cases involved reduction in weekly warfarin dose ranging from 22% to 31%. The Drug Information Probability Score was calculated in six cases, with a score of probable for five cases and possible for one. Very low-quality data support a potential drug-drug interaction with warfarin and both THC and CBD. Clinician recognition of this potential interaction is important. Available evidence supports the need to conduct a drug interaction study between cannabinoids and warfarin to clarify the existence of an interaction.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41139912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Review of anticoagulation considerations in extracorporeal membrane oxygenation support.","authors":"Sydney D T Graboyes, Phillip S Owen, Rickey A Evans, Theodore J Berei, Katarzyna M Hryniewicz, Ian B Hollis","doi":"10.1002/phar.2857","DOIUrl":"10.1002/phar.2857","url":null,"abstract":"<p><p>Since its first success in 1975, extracorporeal membrane oxygenation (ECMO) has been used with increasing frequency for pulmonary and cardiopulmonary bypass. Use in adults has increased exponentially since the early 2000s, but despite thousands of international cannulations using both veno-arterial (VA) and veno-venous (VV) ECMO, there are still significant hemocompatibility-related adverse events. Current management of anticoagulation has been based on the Extracorporeal Life Support Organization guidance published in 2014 with recent updates published in 2022. Despite this guidance, there is still limited international consensus on how to manage anticoagulation in ECMO. For this review, we completed a comprehensive search of multiple electronic databases to identify studies pertaining to anticoagulation of adult patients on VV or VA-ECMO. The highest priority was given to sources that were prospective, randomized, controlled studies, but in the absence of such resources, observational studies, retrospective uncontrolled studies, and case series/reports were considered for inclusion. This document serves to provide a comprehensive review of the current understanding of management pertaining to anticoagulation relating to ECMO.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10339123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transitioning disopyramide to mavacamten in obstructive hypertrophic cardiomyopathy: A case series and clinical guide.","authors":"Andrew Willeford, Jorge Silva Enciso","doi":"10.1002/phar.2874","DOIUrl":"10.1002/phar.2874","url":null,"abstract":"<p><strong>Background: </strong>Hypertrophic cardiomyopathy (HCM) is a genetic disorder for which first-line treatments for obstructive HCM (oHCM) include beta-blockers, non-dihydropyridine calcium channel blockers, and disopyramide for refractory cases. Mavacamten, a selective cardiac myosin inhibitor, is indicated for symptomatic oHCM to improve functional capacity and symptoms. Use of disopyramide and mavacamten together is not recommended due to concerns of additive negative inotropic effects. Transitioning from disopyramide to mavacamten may be preferred to avoid adverse effects and frequent administration, however, the best approach for making the transition has not been established.</p><p><strong>Cases: </strong>We present a series of seven patients with oHCM who transitioned from disopyramide to mavacamten and underwent echocardiograms mandated by a Risk Evaluation and Mitigations Strategies program. Two methods were employed. The first approach, involving washout of disopyramide before starting mavacamten, resulted in worsening of heart failure symptoms in the first two cases. The second approach, involving tapering disopyramide when starting mavacamten, was successfully implemented in the last five cases, with no adverse effects or worsening of systolic dysfunction.</p><p><strong>Conclusion: </strong>Our method of tapering disopyramide when starting mavacamten using a stepwise approach is feasible and safe. Our report fulfills an unmet need by serving as a guide for other clinicians who seek to transition their patients from disopyramide to mavacamten.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10293512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modifiable statin characteristics associated with potential statin-related prescribing cascades.","authors":"Grace Hsin-Min Wang, Earl Morris, Scott M Vouri, Shailina Keshwani, Stephan Schmidt, Carl J Pepine, Steven M Smith","doi":"10.1002/phar.2883","DOIUrl":"10.1002/phar.2883","url":null,"abstract":"<p><strong>Study objective: </strong>Clinicians may prescribe new medications (marker drug) to treat statin-related (index drug) adverse events, constituting a prescribing cascade. We aimed to identify modifiable statin characteristics (intensity and individual statin agents) associated with lower risk of prescribing cascades to inform clinical decisions in the presence of statin-related adverse events.</p><p><strong>Design: </strong>A secondary analysis based on our previous work, a high-throughput sequence symmetry analysis screening for potential statin-related prescribing cascades.</p><p><strong>Data source: </strong>MarketScan Commercial and Medicare Supplemental Insurance claims databases between 2005 and 2019.</p><p><strong>Patients: </strong>Adults who initiated a statin between 2007 and 2018, and who were continuously enrolled in the same healthcare plan for at least 720 days before and 360 days after statin initiation.</p><p><strong>Intervention: </strong>Among the previously identified 57 potential prescribing cascades, 42 statin-marker class dyad with a sample size of ≥ 500 were assessed in this study.</p><p><strong>Measurements: </strong>We measured patients' baseline characteristics within -360 days of statin initiation and reported by modifiable statin characteristics. We also performed logistic regression and reported the adjusted odds ratios (aOR) with 95% confidence intervals (CI) of modifiable statin characteristics after adjusting for baseline characteristics.</p><p><strong>Main results: </strong>We identified 1,307,867 statin initiators who met the study criteria (21% elderly, 52% female). Compared with patients initiating low-intensity statins, those initiating moderate- or high-intensity statins had significantly greater odds to develop 29 (69%) prescribing cascades, including antidiabetic drugs such as dipeptidyl peptidase 4 (DPP-4) inhibitors (aOR 1.22; 95% CI, 1.11-1.35) and glucagon-like peptide-1 (GLP-1) analogs (aOR 1.31; 95% CI, 1.16-1.47), and opioids (aOR 1.18; 95% CI, 1.13-1.23). Individual statin agent selection also had a differential effect on 34 (81%) of the prescribing cascades. For example, compared with simvastatin initiators, the probability of initiating osmotically acting laxatives was significantly higher for lovastatin initiators (aOR 1.09; 95% CI, 1.03-1.15) and significantly lower in atorvastatin initiators (aOR 0.92; 95% CI, 0.89-0.94).</p><p><strong>Conclusion: </strong>Compared with low-intensity statins, high-intensity statins are associated with increased risk in many potential prescribing cascades, while the choice of individual statin agents affects the risk of prescribing cascades bidirectionally.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41123488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Performance of different body weights in the Cockcroft-Gault equation in critically ill patients with and without augmented renal clearance: A multicenter cohort.","authors":"Michaelia D Cucci, Anthony T Gerlach, Caroline Mangira, Claire V Murphy, Jason A Roberts, Andrew A Udy, Thomas C Dowling, Chanda L Mullen","doi":"10.1002/phar.2743","DOIUrl":"10.1002/phar.2743","url":null,"abstract":"<p><strong>Study objective: </strong>The primary objective was to evaluate the performance of the Cockcroft-Gault (CG) equation with different body weights (BWs) compared to a measured creatinine clearance (mCrCl) in an intensive care unit (ICU) population with and without augmented renal clearance (ARC).</p><p><strong>Design: </strong>Multicenter, retrospective cohort.</p><p><strong>Setting: </strong>Two ICUs in the United States and four ICUs from a previous international observational analysis.</p><p><strong>Patients: </strong>Adult ICU patients admitted from January 1, 2010 to July 30, 2020 with at least one mCrCl collected within the initial 10 days of hospitalization were eligible for inclusion.</p><p><strong>Measurements and main results: </strong>The primary outcome was the performance of the CG equation in ARC (mCrCl≥130 ml/min/1.73 m² ) and non-ARC (mCrCl<130 ml/min/1.73 m² ) patients. Correlation was analyzed by Pearson's correlation coefficient, bias by mean difference, and accuracy by the percentage of patients within 30% of the mCrCl. A total of 383 patients were included, which provided 1708 mCrCl values. The majority were male (n = 239, 62%), median age of 55 years [IQR 40-65] with a surgical diagnosis (n = 239, 77%). ARC was identified in 229 (60%) patients. The ARC group had lower Scr values (0.6 [0.5-0.7] vs. 0.7 [0.6-0.9] mg/dl, p < 0.001) and higher mCrCl (172.8 (SD 39.1) vs. 89.9 mL/min/1.73 m² (SD 25.4), p < 0.001) compared with the non-ARC group, respectively. Among non-ARC patients there was a moderate correlation (r = 0.33-0.39), moderate accuracy (range 48-58%), and low bias (range of -12.9 to 17.1) among the different BW estimations with the adjusted BW having the better performance. Among ARC patients there was low correlation (r = 0.24-0.28), low to moderate accuracy (range 38-70%), and high bias (range of -58.5 to -21.6).</p><p><strong>Conclusions: </strong>The CG-adjusted BW had the best performance in the non-ARC patients, while CG performed poorly with any BW in ARC patients. Although the CG equation remains the standard equation for estimating CrCl in the ICU setting, a new, validated equation is needed for patients with ARC.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10947228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40684809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In silico evaluation of a beta-lactam dosing guideline among adults with serious infections.","authors":"Paul Williams, Menino Osbert Cotta, Mohd H Abdul-Aziz, Kathryn Wilks, Andras Farkas, Jason A Roberts","doi":"10.1002/phar.2753","DOIUrl":"10.1002/phar.2753","url":null,"abstract":"<p><strong>Study objective: </strong>The aim of this study was to compare the achievement of therapeutic pharmacokinetic-pharmacodynamic (PK-PD) exposure targets for beta-lactam antibiotics using product information dosing or guideline-based dosing for the treatment of serious infections.</p><p><strong>Design: </strong>In silico study.</p><p><strong>Data source: </strong>ID-ODS^TM (Individually Designed Optimum Dosing Strategies).</p><p><strong>Patients and intervention: </strong>None.</p><p><strong>Measurements and main results: </strong>In silico product information and guideline-based dosing simulations for cefepime, ceftazidime, flucloxacillin, meropenem, and piperacillin/tazobactam were performed using pharmacokinetic models from seriously ill patient populations. The median simulated concentration at 48 and 96 h was used to measure the probability of target attainment (PTA) to achieve predefined therapeutic and toxicity PK-PD targets. A multiple linear regression model was constructed to identify the effect of guideline-based dosing covariates on achieving pre-defined therapeutic targets. In total, 480 dosing simulations were performed. The PTA percentage with guideline-based dosing at 48 and 96 h was 80% and 68%, respectively, yielding significantly higher results when compared to product information dosing (48.45% and 49%, respectively), p < 0.001 at both time points. At 48 h, predefined toxicity thresholds were exceeded in 4.7% and 0% of simulations for guideline-based and product information-based dosing, respectively (p = 0.002). eGFR was significantly associated with the % PTA by guideline-based dosing, with eGFR values of 20 and 50 ml/min both statistically significant in leading to an increase in PTA.</p><p><strong>Conclusions: </strong>Our study demonstrated that achievement of PK-PD exposures associated with an increased likelihood of effectiveness was more likely to occur with guideline-based dosing; especially at 48 h.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10946580/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9088549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}