Antifungal Pharmacokinetics and Dosing Considerations in Burn Patients

Patients with burn injuries are at high risk of developing invasive fungal infections leading to increased morbidity and mortality. Burn patients undergo major physiologic changes, which produce significant alterations in the pharmacokinetics and pharmacodynamics of antimicrobial agents. These changes result from the breakdown of the body’s natural barriers to infection and the systemic responses that subsequently ensue after burn injury, including systemic inflammatory responses, third spacing, and development of a hypermetabolic state. Severe burn injuries often lead to larger volumes of distribution and increased drug clearance. Limited data are available to guide the clinician in optimizing the dosing regimen of antifungals in patients with burn injuries. We present a review of antifungal pharmacokinetics and describe how these properties can be used to design rational therapeutic regimens tailored to the pharmacodynamic alterations characteristic of burn patients.     

恶性血液病患者外周血淋巴细胞亚群变化及其临床意义的研究

目的: 探讨恶性血液病外周血淋巴细胞亚群变化特征及临床意义。方法: 采用流式细胞仪检测64例初诊的血液系统恶性肿瘤患者的外周血淋巴细胞亚群。病种包括急性髓系白血病(acute myeloid leukemia,AML)、急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)、霍奇金淋巴瘤(Hodgkin’s lymphoma,HL)、非霍奇金淋巴瘤(Non-Hodgkinlymphoma,NHL)。分析比较30例正常人的外周血淋巴细胞亚群与实验组的差异,并对64例恶性血液病患者中连续动态监测的21例急性白血病患者外周血淋巴细胞亚群结果变化与预后关系进行分析。结果： 不同成人恶性血液病患者年龄分组淋巴细胞亚群变化无明显差异;恶性血液病患者中CD3 ⁺CD8 ⁺ T淋巴细胞百分比、Treg细胞百分比均增加;CD16 ⁺/CD56 ⁺NK细胞百分比及CD4 ⁺/CD8 ⁺比值均下降;CD3 ⁺T淋巴细胞数量、CD3 ⁺CD4 ⁺淋巴细胞数、CD3 ⁺CD8 ⁺淋巴细胞数量、CD3 ^-CD19 ⁺淋巴细胞数量、CD16 ⁺/CD56 ⁺NK淋巴细胞数量及CD4 ⁺/CD8 ⁺比值均减少;急性白血病及恶性淋巴瘤患者外周血淋巴细胞亚群与正常对照组比较存在一定的差异;急性白血病未缓解组的Treg细胞比例明显高于急性白血病首疗程缓解组及对照组;急性白血病复发组Treg细胞比例明显高于急性白血病持续缓解组以及对照组;对21例急性白血病患者动态监测的淋巴细胞亚群发现,化疗缓解的患者Treg在化疗过程中逐渐下降,至第3~6个疗程逐渐接近正常对照,化疗未缓解的患者Treg细胞在化疗过程中逐渐上升或持续大于10%,明显高于完全缓解组,复发患者Treg在化疗过程中先下降后明显上升。 结论： 恶性血液病患者免疫功能显著低于健康人,且伴随免疫功能紊乱,且不同疾病类型、不同的疾病状态免疫紊乱的程度不一,Treg细胞比例可以用来预测急性白血病患者疗效及复发,可以为患者的临床治疗方案及用药强度提供指导依据。     

Management of Hyperglycemia in Diabetic Patients with Hematologic Malignancies During Dexamethasone Therapy

ObjectiveTo compare the response to different insulin regimens for management of hyperglycemia in diabetic patients with hematologic malignancies who are receiving dexamethasone.MethodsA retrospective analysis was conducted to determine whether a basal bolus insulin (BBI) regimen with detemir and aspart is superior to a sliding scale regular insulin (SSI) regimen for management of hyperglycemia in hospitalized diabetic patients receiving dexamethasone.ResultsForty patients with hematologic malignancies were treated with intravenous (8 to 12 mg/day) or oral (40 mg/day) dexamethasone for 3 days. The average blood glucose (BG) level was 301 ± 57 mg/dL in the SSI group (n = 28) and 219 ± 51 mg/dL in the BBI group (n = 12) (P <.001). The BBI regimen resulted in an average BG reduction of 52 ± 82 mg/dL throughout the course of dexa-methasone therapy, while the SSI regimen produced an increase in the mean daily BG level of 128 ± 77 mg/dL (P <.001). On the last day of dexamethasone administration, the insulin requirement was 49 ± 29 units/day in the SSI group and 122 ± 39 units/day in the BBI group (P <.001). Three patients in the SSI group developed diabetic ketoacidosis or hyperosmolar hyperglycemia during steroid therapy. No hypoglycemia was observed in either group. The length of stay and infection rates were similar between groups.ConclusionBasal and bolus insulin regimen is an effective and safe approach for managing dexamethasone-induced hyperglycemia in hospitalized patients with hematologic malignancies. (Endocr Pract. 2013;19:231-235)     

Effect of the Current Antimicrobial Therapeutic Strategy on Fungal Colonization in Patients with Hematologic Malignancies

A “quasi-experimental” trial was carried out to investigate the effect of three antimicrobial regimens on oral and fecal yeast colonization in patients with hematologic malignancies. Fifty-four patients received ciprofloxacin and oral amphotericin B (group 1); 45 received ceftazidime, amikacin, vancomycin, and oral amphotericin B (group 2); and 30 received ceftazidime, amikacin, vancomycin, and intravenous amphotericin B (group 3). The oral yeast isolation rate showed a decrease in group 1 (from 59.3% to 40.7%) and group 3 (from 56.7% to 46.7%), and a marked increase in group 2 (from 51.1% to 84.4%). All the groups showed a reduction in their fecal yeast isolation rate. An overgrowth of Candida parapsilosis, C. krusei, and C. tropicalis was observed in all the groups, but it was much higher in group 2. Our findings provide evidence that ceftazidime, amikacin, and vancomycin, given with oral amphotericin B, induce an overgrowth/persistence of Candida species in the mouth and gut, which might be attributable to inclusion of vancomycin. Treatment with intravenous amphotericin B has at least the capacity of counterbalancing yeast proliferation induced by that antibacterial regimen. Received: 27 November 1995 / Accepted: 22 January 1996     

Pharmacokinetics and metabolism of RU 486

The effects of dose on the initial pharmacokinetics and metabolism of an antiprogesterone steroid RU 486 (mifepristone) were studied in healthy female volunteers after administration of RU 486 as a single dose of 50-800 mg. The concentrations of RU 486 and its monodemethylated, dimethylated and hydroxylated non-demethylated metabolites were measured specifically after Chromosorb-column chromatography by HPLC. Their relative binding affinities to the human uterine progesterone receptor were also determined. Micromolar concentrations of the parent compound in blood were reached within the first hour after oral administration. The pharmacokinetics of RU 486 followed two distinct patterns in a dose-dependent fashion. With a low dose of 50 mg the pharmacokinetics followed an open two-compartment model with a half-life of over 27 h. With the doses of 100-800 mg the initial redistribution phase of 6-10 h was followed by zero-order kinetics up to 24 h or more. Importantly, after ingestion of doses higher than 100 mg of RU 486 there were no significant differences in plasma concentrations of RU 486 within the first 48 h, with the exception of plasma RU 486 concentrations at 2 h. After single oral administration of 200 mg unchanged RU 486 was found 10 days later in two subjects. The elimination phase half-life with this dose, calculated between day 5 and 6, was 24 h. Micromolar concentrations of monodemethylated, didemethylated and non-demethylated hydroxylated metabolites were measured within 1 h after oral administration of RU 486. In contrast to plasma RU 486 concentrations, circulating plasma concentrations of metabolites increased in a dose-dependent fashion. With higher doses the metabolite concentrations were close to, or even in excess to the parent compound. The relative binding affinities of RU 486, monodemethylated, didemethylated and hydroxylated metabolites (progesterone = 100%) to the human progesterone receptor were 232, 50, 21, and 36, respectively. The existence of a high affinity-limited capacity serum binding protein would explain the long half-life and the observed diverging dose-dependent pharmacokinetics. The extravasation of RU 486 after the saturation of serum binding sites would explain the blunted serum peak concentrations of RU 486 with higher doses. The return of the drug back to circulation thereafter explains the zero-order kinetics. High concentrations of circulating metabolites capable of binding to the progesterone receptor suggest a significant contribution of these steroids in the overall antiprogestational action.     

Hemoglobin Maintenance with use of Extended Dosing of Epoetin Alfa in Patients with Diabetes and Anemia of Chronic Kidney Disease

ObjectiveTo compare the efficacy of extended epo-etin alfa dosing in maintaining hemoglobin (Hb) concentrations in patients with and without diabetes as the primary cause of chronic kidney disease.MethodsWe undertook a post hoc analysis of the Clinical Evaluation of PROCRIT® for Maintenance Phase Treatment of Patients With Anemia Due to Chronic Kidney Disease (PROMPT) study. The study patients had chronic kidney disease but were not receiving dialysis, had stable Hb levels of ≥ 11.0 g/dL, and had been receiving epoetin alfa for ≥ 2 months. Patients received 1 of 4 epoetin alfa dosing regimens administered subcutaneously for up to 16 weeks: 10,000 U once weekly (QW), 20,000 U every 2 weeks (Q2W), 30,000 U every 3 weeks (Q3W), or 40,000 U every 4 weeks (Q4W). The primary end point was the percentage of patients able to achieve Hb maintenance, defined as a mean Hb level of ≥ 11.0 g/dL from week 2 to final measurement.ResultsAmong 445 evaluable patients, 201 had diabetes and 244 did not have diabetes. Mean baseline Hb was 11.9 g/dL in both groups. The percentage of patients achieving Hb maintenance, stratified by epoetin alfa dosing regimen, was similar in patients with and those without diabetes: QW (90.2% versus 96.5%), Q2W (91.1% versus 87.9%), Q3W (80.0% versus 75.7%), or Q4W (79.2% versus 72.5%). The incidence of adverse events was low and comparable between patients with and those without diabetes.ConclusionApproximately 90% of patients with and without diabetes in the QW and Q2W groups and more than 70% in the Q3W and Q4W groups maintained mean Hb levels of ≥ 11.0 g/dL from week 2 to final measurement. These results demonstrated that patients with diabetes responded in a similar manner as patients without diabetes to extended dosing of epoetin alfa up to Q4W. (Endocr Pract. 2007;13:251-259)     

Cryptococcosis in Patients with Hematologic Diseases

Purpose of Review

In this paper, we reviewed the epidemiology, diagnosis, and treatment of cryptococcosis in patients with hematologic malignancies. We reviewed all case series of cryptococcosis in different hematologic conditions, and looked at epidemiologic trends considering the new antineoplastic drugs introduced in the treatment of hematologic malignancies.

Recent Findings

Case series of cryptococcosis in patients with hematologic malignancies are scarce. We identified an increase in the proportion of cases of cryptococcosis occurring in patients with hematologic malignancies, and many case reports of cryptococcosis in patients receiving ibrutinib, a Bruton kinase inhibitor used in the treatment of chronic lymphoproliferative diseases.

Summary

Cryptococcosis is uncommon in patients with hematologic malignancies, but its occurrence may be associated with poor outcome. Hematologists should be aware of this complication if patients develop neurologic symptoms or present with pulmonary infiltrates that do not improve with antibiotics.

     

Hyperuricemia in Hematologic Malignancies Is Caused by an Insufficient Urinary Excretion

In order to elucidate the mechanism of hyperuricemia in hematologic malignancies, we have retrospectively investigated the uric acid metabolism in 418 chemotherapy-naïve patients with hematologic malignancies. Hyperuricemia was present in 116 (27.8%) of these patients on initial hospitalization. Among 65 hyperuricemic patients analyzed uric acid metabolism, six (9.2%) had overproduction type, 52 (80.0%) had underexcretion type, and seven (10.8%) had a mixed type. Fourteen patients (3.3%) developed tumor lysis syndrome in 418 patients.     

Vancomycin Dosing in Neutropenic Patients

Background

To compare vancomycin pharmacokinetic parameters in patients with and without neutropenia.

Methods

Patients ≥18 years admitted on general wards were included. Routinely vancomycin trough and peak plasma concentrations were measured with a fluorescence polarization immunoassay. Pharmacokinetic parameters of individual patients were determined with maximum a posterior Bayesian estimation (MW Pharm 3.60). Neutropenia was defined as neutrophils <0.5×10⁹ cells/L.

Principal Findings

A total of 171 patients were included. Patients with neutropenia (n = 56) had higher clearance of vancomycin (CLva), 67 (±26) mL/min, compared to patients without neutropenia (n = 115), CLva 50 (±22) mL/min (p<0.001). No significant difference was found in serum creatinine and vancomycin volume of distribution. Neutropenia was positively associated with CLva, independently of relevant co-variables (B: 12.122, 95%CI: 1.095 to 23.149, p = 0.031). On average patients with neutropenia needed 33% higher doses of vancomycin to attain adequate exposure, i.e. AUC₂₄≥400 mg×h/L. Furthermore, 15 initially neutropenic patients in our study group received vancomycin for a second administration period. Ten patients received the second administration period during another neutropenic period and 5 patients during a non-neutropenic phase. All 5 patients with vancomycin during both neutropenic and non-neutropenic phase had higher CLva (91 (±26) mL/min) during the neutropenic period and lower CLva (45 (±10) mL/min) during the non-neutropenic phase (p = 0.009).

Conclusion

This study shows that most patients with neutropenia have augmented CLva. In a small group of patients that received vancomycin during two episodes, the augmented CLva seems to be reversible in the non-neutropenic period. Our data indicate that it is important to increase the daily dose with one third in patients with neutropenia (from 15 mg/kg twice daily to 13 mg/kg three times daily). Frequent performance of therapeutic drug monitoring in patients with neutropenia may prevent both therapy failure due to low AUCs and overcomes toxicity due to high vancomycin trough concentrations during recovery from neutropenia.     

Detection and Identification of Hematologic Malignancies and Solid Tumors by an Electrochemical Technique

PurposeDevelop and evaluate an electrochemical method to identify healthy individuals, malignant hematopathic patients and solid tumor patients by detecting the leukocytes in whole-blood.MethodsA total of 114 individual blood samples obtained from our affiliated hospital in China (June 2015- August 2015) were divided into three groups: healthy individuals (n = 35), hematologic malignancies (n = 41) and solid tumors (n = 38). An electrochemical workstation system was used to measure differential pulse voltammetry due to the different electrochemical behaviors of leukocytes in blood samples. Then, one-way analysis of variance (ANOVA) was applied to analyze the scanning curves and to compare the peak potential and peak current.ResultsThe scanning curve demonstrated the specific electrochemical behaviors of the blank potassium ferricyanide solution and that mixed with blood samples in different groups. Significant differences in mean peak potentials of mixture and shifts (ΔEp (mV)) were observed of the three groups (P< = 0.001). 106.00±9.00 and 3.14±7.48 for Group healthy individuals, 120.90±11.18 and 18.10±8.81 for Group hematologic malignancies, 136.84±11.53 and 32.89±10.50 for Group solid tumors, respectively. In contrast, there were no significant differences in the peak currents and shifts.ConclusionsThe newly developed method to apply the electrochemical workstation system to identify hematologic malignancies and solid tumors with good sensitivity and specificity might be effective, suggesting a potential utility in clinical application.     

Antifungal Dosing in Critically Ill Patients

This article reviews appropriate dosing for antifungals and emphasizes factors specific to the critically ill patient, along with drug pharmacokinetics and pharmacodynamics. The rationale for doses of the echinocandins (caspofungin, micafungin, anidulafungin), triazoles (fluconazole, voriconazole, itraconazole, posaconazole), amphotericin B (including lipid formulations), and flucytosine are discussed.     

Influence of Time of Day on Propofol Pharmacokinetics and Pharmacodynamics in Rabbits

This study evaluates the administration time-of-day effects on propofol pharmacokinetics and sedative response in rabbits. Nine rabbits were sedated with 5?mg/kg propofol at three local clock times: 10:00, 16:00, and 22:00?h. Each rabbit served as its own control by being given a single infusion at the three different times of day on three separate occasions. Ten arterial blood samples were collected during each clock-time experiment for propofol assay. A two-compartment model was used to describe propofol pharmacokinetics, and the pedal withdrawal reflex was used as the sedation pharmacodynamic response. The categorical data comprising the presence or absence of pedal withdrawal reflex was described by a logistic model. The typical volume of the central compartment equaled 7.67?L and depended on rabbit body weight. The elimination rate constant depended on drug administration time; it was lowest at 10:00?h, highest at 16:00?h, and intermediate at 22:00?h. Delay of the anesthetic effect, with respect to plasma concentrations, was described by the effect compartment, with the rate constant for the distribution to the effector compartment equal to 0.335?min^?1. Drug concentration had a large effect on the probability of anesthesia. The degree of anesthesia was largest at 10:00?h, lowest at 16:00?h, and intermediate at 22:00?h. In summary, both the pharmacokinetics and pharmacodynamics of propofol in rabbits depended on administration time. The developed population approach may be used to assess chronopharmacokinetics and chronopharmacodynamics of medications in animals and humans. (Author correspondence: agnbienert@op.pl)     

血液病患者院内感染危险因素分析与对策

目的：探讨血液病患者院内感染危险因素,为制定控制措施提供理论依据。方法：回顾性调查我院血液科2009年3月．2011年3月间685例血液病患者发生院内感染的情况,并对引起院内感染的危险因素进行分析。结果：685例患者中有91例发生院内感染,感染部位以呼吸系统、皮肤和口腔为主。分离病原菌88株,革兰阴性杆菌53株（60．22％）,革兰阳性菌28株（31．81％）,真菌7株（7．95％）。白细胞下降、化疗、激素和广谱抗生素的使用是院内感染的主要因素。结论：为减少医院感染发生率,必须对白细胞〈2×10^9／L的病人进行保护性隔离,并合理使用抗生素治疗感染性疾病。     

血液病患者院内感染危险因素分析与对策

目的:探讨血液病患者院内感染危险因素,为制定控制措施提供理论依据。方法:回顾性调查我院血液科2009年3月-2011年3月间685例血液病患者发生院内感染的情况,并对引起院内感染的危险因素进行分析。结果:685例患者中有91例发生院内感染,感染部位以呼吸系统、皮肤和口腔为主。分离病原菌88株,革兰阴性杆菌53株(60.22%),革兰阳性菌28株(31.81%),真菌7株(7.95%)。白细胞下降、化疗、激素和广谱抗生素的使用是院内感染的主要因素。结论:为减少医院感染发生率,必须对白细胞<2×109/L的病人进行保护性隔离,并合理使用抗生素治疗感染性疾病。     

转录因子YY1的结构、调控及其在血液肿瘤中的研究进展

转录因子Yin Yang(YY)1在多种组织中广泛表达,YY1通过影响细胞增殖、凋亡及分化等生命过程,从而在生物体内发挥着重要作用。YY1具有复杂的转录调控机制,依赖于接触不同的蛋白辅助因子,可激活或抑制相关基因。已有大量有关YY1在各种肿瘤,如淋巴瘤、白血病、前列腺癌、乳腺癌、宫颈癌、结肠癌等中表达及调控机制的研究,结果表明YY1在绝大多数肿瘤中异常高表达,并且与其肿瘤的形成、进展及不良预后有关。本文从YY1的基因结构及调控机制入手,集中阐述YY1与血液肿瘤相关的研究进展,对其在常见血液肿瘤中的表达、功能及预后等关系等作一综述。     

GM抗原检测对血液病患者侵袭性曲霉病的诊断价值

目的:探讨血清半乳甘露聚糖(GM)抗原检测对于血液病患者侵袭性曲霉病(invasive aspergillosis,IA)的早期诊断和疗效评价的临床意义。方法:选取137例具有侵袭性真菌病IFD高危因素患者的468份血清标本,进行GM试验,检测抗真菌治疗前后GM抗原水平的变化,同时收集患者的临床资料,进行统计学分析,并评价GM检测对于血液病患者IA的诊断价值。结果:以GM检测单次I≥1.0作为阳性界值时,本试验的敏感性、特异性、阳性预测值和阴性预测值分别为90.91%,95.65%95.24%和91.67%,与试剂盒提供的血清GM试验结果的单次I≥1.5的阳性界值相比敏感性明显提高,而特异性无明显降低,因此能够有效区分临床诊断和拟诊两个IA级别。在其他实验室检测和影像学检查的基础上加入GM试验后,IA临床诊断组的人数明显增加。诊断级别与I值总体均数的分布具有相关性,回顾性确诊IA组、回顾性可疑IA组、回顾性排除IA组的I值呈现明显的由高到低的群落分布,且三个诊断级别的I值分布范围的差异有统计学意义。根据阳性界值标准I≥1.0,GM试验阳性早于痰培养阳性平均7.73±8.71 d,也早于CT影像学证据平均6.89±8.02 d。基于GM值阳性时的抢先抗曲霉治疗组的有效率明显提高(P=0.039)。结论:血清GM抗原检测是早期诊断IA的一种有效方法,将单次I≥1.0作为阳性界值具有较好的敏感性和特异性,在阳性检出率和阳性检出时间方面较主要影像学表现和微生物学证据具有一定优势。在高危血液病伴粒细胞缺乏患者中根据GM试验阳性进行抢先抗曲霉治疗,可提高治疗有效率,监测血清GM浓度的动态变化具有评价疗效的重要价值。该研究成果对临床侵袭性曲霉病的诊断和治疗具有一定指导意义。     

顺式阿曲库铵对阻塞性黄疸患者麻醉的药效学研究

目的:观察非去极化肌松药顺式阿曲库铵用于阻塞性黄疸患者麻醉中的肌松效应和安全性.方法:24例阻塞性黄疸患者行胆总管引流术,随机分为顺式阿曲库铵Ⅰ组(2倍ED95组)、Ⅱ组(3倍ED95组),24例切口部位相近行上腹部手术患者随机分为顺式阿曲库铵Ⅲ组(2倍ED95组)、Ⅳ组(3倍ED95组)作为对照.观察诱导前后生命体征的变化、插管条件、肌松效应.结果:各组患者的血流动力学变化:组间比较无显著性差异(P>0.05);Ⅰ、Ⅲ组插管条件为优的比率明显低于Ⅱ、Ⅳ组(P<0.05);Ⅰ组、Ⅲ组起效时间大于Ⅱ组、Ⅳ组,但是T195%恢复时间、四个成串刺激(TOF)比值恢复到70%的时间明显短于Ⅱ组、Ⅳ组(P<0.05).结论:顺式阿曲库铵可以安全用于阻塞性黄疸患者的麻醉,3ED95剂量的顺式阿曲库铵比2ED95剂量的起效更快,插管条件更好.     

Adherence with Dosing Guideline in Patients with Impaired Renal Function at Hospital Discharge

Objectives

To determine the prevalence, determinants, and potential clinical relevance of adherence with the Dutch dosing guideline in patients with impaired renal function at hospital discharge.

Design

Retrospective cohort study between January 2007 and July 2011.

Setting

Academic teaching hospital in the Netherlands.

Subjects

Patients with an estimated glomerular filtration rate (eGFR) between 10-50 ml/min/1.73m² at discharge and prescribed one or more medicines of which the dose is renal function dependent.

Main Outcome Measures

The prevalence of adherence with the Dutch renal dosing guideline was investigated, and the influence of possible determinants, such as reporting the eGFR and severity of renal impairment (severe: eGFR<30 and moderate: eGFR 30-50 ml/min/1.73m²). Furthermore, the potential clinical relevance of non-adherence was assessed.

Results

1327 patients were included, mean age 67 years, mean eGFR 38 ml/min/1.73m². Adherence with the guideline was present in 53.9% (n=715) of patients. Reporting the eGFR, which was incorporated since April 2009, resulted in more adherence with the guideline: 50.7% vs. 57.0%, RR 1.12 (95% CI 1.02-1.25). Adherence was less in patients with severe renal impairment (46.0%), compared to patients with moderate renal impairment (58.1%, RR 0.79; 95% CI 0.70-0.89). 71.4% of the cases of non-adherence had the potential to cause moderate to severe harm.

Conclusion

Required dosage adjustments in case of impaired renal function are often not performed at hospital discharge, which may cause harm to the majority of patients. Reporting the eGFR can be a small and simple first step to improve adherence with dosing guidelines.     

替考拉宁在感染的血液病患者中血药浓度的监测与应用价值分析

目的:探讨替考拉宁在感染的血液病患者中血药浓度的监测与应用价值.方法:回顾分析2017年12月-2019年12月来我院治疗的42例革兰氏阳性球菌引起感染的血液病患者临床资料,按照临床替考拉宁的给药剂量分A组和B组,每组21例.利用高效液相色谱法(HPLC)检测患者第5天用药前30 min的血药浓度,利用酶联免疫荧光法检...     

Dosing Common Medications in Hospitalized Pediatric Patients with Obesity: A Review

Medication management in children and adolescents with obesity is challenging because both developmental and pathophysiological changes may impact drug disposition and response. Evidence to date indicates an effect of obesity on drug disposition for certain drugs used in this population. This work identified published studies evaluating drug dosing, pharmacokinetics (PK), and effect in pediatric patients with obesity, focusing on 70 common medications used in a pediatric network of 42 US medical centers. A PubMed search revealed 33 studies providing PK and/or effectiveness data for 23% (16 of 70) of medications, 44% of which have just one study and can be considered exploratory. This work appraising 4 decades of literature shows several promising approaches: greater use of PK models applied to prospective clinical studies, dosing recommendations derived from both PK and safety, and multiyear effectiveness data on drugs for chronic conditions (e.g., asthma). Most studies make dose recommendations but are weakened by retrospective study design, small study populations, and no controls or historic controls. Dosing decisions continue to rely on extrapolating knowledge, including targeting systemic drug exposure typically achieved in adults. Optimal weight‐based dosing strategies vary by drug and warrant prospective, controlled studies incorporating PK and modeling and simulation to complement clinical assessment.