scholarly journals An Evaluation of Initial Vancomycin Dosing in Infants, Children, and Adolescents

2011 ◽  
Vol 2011 ◽  
pp. 1-4 ◽  
Author(s):  
Laura Broome ◽  
Tsz-Yin So
Keyword(s):  
Primary Outcome ◽  
Age Groups ◽  
Pediatric Age ◽  
Serum Trough ◽  
Hospital Patients ◽  
Dosing Regimens ◽  
Dosing Strategies ◽  
Trough Concentrations ◽  
Higher Doses ◽  
Retrospective Database

Background. The pharmacokinetics of many medications change as we age, thus most would assume dosing strategies would adjust for these changes. The objective of this study is to evaluate the initial vancomycin dosing in three pediatric age groups based on measured serum trough concentrations.Methodology. This retrospective database review included patients aged from 1 month to 18 years old admitted to the Moses H. Cone Memorial Hospital. Patients had to have received vancomycin dosed at 15 mg/kg every 8 hours with an appropriately measured trough concentration. The primary outcome was to determine the percentage of patients in 3 pediatric age groups achieving therapeutic trough concentrations with the initial vancomycin dosing regimen.Results. Twenty-five patients were included in the study. None of the patients had therapeutic trough concentrations after receiving vancomycin 15 mg/kg every 8 hours. Only one patient had a supratherapeutic level, while all of the other patients had levels less than 10 mcg/mL.Conclusions. Vancomycin 15 mg/kg every 8 hours did not provide therapeutic serum trough concentrations for any pediatric age groups. Higher doses and/or more frequent dosing regimens need to be evaluated for each age group to determine the most appropriate strategies for producing therapeutic trough concentrations.

scholarly journals CYP2C19 phenotype and body-weight-guided voriconazole initial dose in infants and children after hematopoietic cell transplantation

2021 ◽  
Author(s):  
Takuto Takahashi ◽  
Maryam A. Mohamud ◽  
Angela R. Smith ◽  
Pamala A. Jacobson ◽  
Mutaz M. Jaber ◽  
...  
Keyword(s):  
Body Weight ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Age Groups ◽  
Model Performance ◽  
Therapeutic Index ◽  
Hematopoietic Cell ◽  
Therapeutic Drug ◽  
Dosing Regimens ◽  
Trough Concentrations

Background : Prophylactic voriconazole use is recommended in children undergoing hematopoietic cell transplantation (HCT). Dosing considerations are essential due to its narrow therapeutic index. Known covariates do not sufficiently explain large interindividual pharmacokinetic (PK) variability of voriconazole. Moreover, knowledge of voriconazole PK for age <2 years is limited. Objectives : We investigated genetic and clinical covariate association with voriconazole interindividual PK variability and subsequently simulated dosing regimens in children. Methods : This study was conducted as a part of a single-institution, phase I study of intravenous voriconazole in children undergoing HCT. We conducted a population PK analysis and tested covariate effects on voriconazole PK, including 67 genetic variants and clinical variables. Results : We analyzed plasma voriconazole and n-oxide metabolite concentrations from 58 children aged <21 years (n=12 in age <2 years). A two-compartment parent mixed linear/nonlinear model best described our data. CYP2C19 phenotype and body weight were significant covariates (both p<0.05). Our model performance in age <2 years was comparable to other age groups. Simulation of the final model suggested the following dosages to attain target steady-state trough concentrations of 1.5 - 5.0 mg/L in CYP2C19 normal phenotype: 16 mg/kg (weight <15 kg), 12 mg/kg (weight 15-30 kg), 10 mg/kg (weight >30 kg), whereas dosages were 33-50% lower for CYP2C19 poor/intermediate and 25-50% higher for CYP2C19 rapid/ultrarapid phenotypes. Conclusions : We propose a new starting dosage regimen, combined with therapeutic drug monitoring for intravenous voriconazole in children of all ages. Future studies should validate this dosing regimen.

scholarly journals Evaluation of Posaconazole Dosing in Children and Young Adults: A Single-Center Review

2021 ◽  
Vol 26 (8) ◽  
pp. 834-840
Author(s):  
Lauren M. Garner ◽  
Susan Ngo ◽  
Jenna Bognaski Kaplan ◽  
William S. Wilson ◽  
Cameron J. McKinzie
Keyword(s):  
Pediatric Patients ◽  
Liver Function Tests ◽  
Current Data ◽  
Dosing Regimen ◽  
Drug Concentrations ◽  
Dosing Regimens ◽  
Dosing Strategies ◽  
Trough Concentrations ◽  
Dosing Strategy ◽  
Dose Modifications

OBJECTIVE Initial posaconazole dosing regimens in children often do not achieve target concentrations, and data continue to support the need for higher initial dosing regimens. The objective of this study is to contribute to the current data regarding suboptimal posaconazole dosing in pediatric patients by retrospectively observing dosing strategies and subsequent drug concentrations. METHODS This study was conducted at a single institution in 27 patients aged 1 to 21 years. Patients who were initiated on any formulation of posaconazole for prophylaxis or treatment while admitted to the hospital were included. The primary outcome was to determine the percentage of pediatric patients who achieved the targeted trough concentration using their initial posaconazole dosing regimen. Secondary outcomes included percentage of patients who experienced a breakthrough invasive fungal infection (IFI), percentage of patients with elevated liver function tests (LFTs), and discontinuation for any reason. RESULTS There were 15 patients (55.5%) who reached desired trough serum concentration after the initial dosing regimen. The number of dose modifications to achieve the desired trough ranged from 1 to 3. Most patients received delayed-release tablets (n = 17), and the average doses for reaching prophylactic and treatment trough concentrations were 6.1 mg/kg/day and 11 mg/kg/day, respectively. There were 2 patients (7.4%) who experienced breakthrough IFI. Overall, 5 patients developed elevated LFTs and 7 patients discontinued treatment early. CONCLUSIONS The results describe a single population of pediatric patients, of whom 55% were able to achieve target trough concentrations of posaconazole with the initial dosing strategy used.

Enoxaparin Dosing at Extremes of Weight: Literature Review and Dosing Recommendations

2018 ◽  
Vol 52 (9) ◽  
pp. 898-909 ◽  
Author(s):  
Jamie Sebaaly ◽  
Kelly Covert
Keyword(s):  
Body Weight ◽  
Data Extraction ◽  
Vte Prophylaxis ◽  
High Body Weight ◽  
High Body ◽  
Study Selection ◽  
Treatment Dose ◽  
Dosing Regimens ◽  
Dosing Strategies ◽  
Higher Doses

Objective: To review the literature on both thromboprophylaxis and treatment of venous thromboembolism (VTE) with enoxaparin in low- and high-body-weight patients and to make dosing and monitoring recommendations in these patient populations. Data Sources: A search using PubMed was conducted (1995 to January 2018) using the following key words: enoxaparin, body weight, AND thromboprophylaxis, or AND treatment. Additional references were identified from a review of citations. Study Selection and Data Extraction: Studies included examined the effect of body weight and/or body mass index (BMI) on VTE, bleeding, enoxaparin dosing, and/or anti-Xa concentrations for thromboprophylaxis and treatment-dose enoxaparin. Studies in pediatric and pregnant patients were excluded. Data Synthesis: Optimal enoxaparin dosing strategies for VTE prophylaxis and treatment for patients at extremes of weight have not yet been elucidated by clinical trials; however, data suggest that standard dosing regimens may not be appropriate in these patients. Relevance to Patient Care and Clinical Practice: This review provides a thorough discussion on both thromboprophylaxis and treatment of VTE with enoxaparin in low- and high-body-weight patients. It includes dosing recommendations to guide clinicians caring for these patient populations. Conclusions: Patients at extremes of weight require special consideration to determine appropriate enoxaparin doses. Specifically, low-body-weight patients may benefit from 30 mg subcutaneously daily for VTE prophylaxis, and standard weight-based dosing for VTE treatment. Conversely, in patients with BMIs ≥40 kg/m2, 40 mg subcutaneously twice daily is recommended, with consideration for higher doses in patients with BMIs ≥50 kg/m2.

scholarly journals DOSE-EXPOSURE SIMULATION FOR PIPERACILLIN-TAZOBACTAM DOSING STRATEGIES IN INFANTS AND YOUNG CHILDREN

2017 ◽  
Vol 24 (3) ◽  
pp. e33-e44
Author(s):  
Céline Thibault ◽  
Nastya Kassir ◽  
Yves Théorêt ◽  
France Varin ◽  
Catherine Litalien ◽  
...  
Keyword(s):  
Age Groups ◽  
Volume Of Distribution ◽  
Distribution Data ◽  
Parameter Estimates ◽  
Target Attainment ◽  
Minimal Inhibitory Concentrations ◽  
Dosing Regimens ◽  
Dosing Strategies ◽  
Post Hoc ◽  
Infants And Young Children

Background: Extended piperacillin-tazobactam (TZP) infusions have been associated with favorable outcomes. There are currently no pediatric dosing recommendations. Objective: To determine appropriate TZP dosing strategies in children 2 months – 6 years according to age and different minimal inhibitory concentrations (MICs). Methods: Age and weight were simulated for 1000 children. Post-hoc pharmacokinetic parameter estimates were generated using published clearance and volume of distribution data. For different dosing regimens, we estimated the probability of target attainment (PTA) over a range of MICs from 4 to 128 mg/L. The pharmacodynamic (PD) target was defined as free piperacillin concentrations above the MIC for ≥ 50% of the dosing interval. A PTA ≥ 90% was defined as optimal. Results: PTA decreased as MIC and age increased. In all age groups, standard dosing regimens (240-300 mg/kg/day, 0.5h infusions) failed to reach PTAs ≥ 90% at MICs ≥ 16 mg/L. Standard 0.5h infusions reached PTAs ≥ 90% at MICs up to 8 mg/L in infants > 2 to 6m. No 0.5h infusion reached PTAs ≥ 90% for MICs ≥ 4 mg/L in children > 6m. While none of the tested regimens were optimal at MICs > 16 mg/L in children > 6m, 100 mg/kg/dose every 6h as a 3h infusion reached PD target at MICs of 32 mg/L in infants > 2 to 6m. Conclusion: Up to MICs of 16 mg/L, 90 mg/kg/dose every 8h as a 2h infusion in infants > 2 to 6m and 100 mg/kg/dose every 8h as a 4h infusion in children > 6m-6y achieved PTAs ≥ 90%.

Effect of Vasopressin Dose on Hemodynamic Response in Obese Patients With Septic Shock: A Retrospective Observational Study

2021 ◽  
pp. 106002802110072
Author(s):  
Casey A. Dubrawka ◽  
Kevin D. Betthauser ◽  
Hannah E. Pope ◽  
Gabrielle A. Gibson
Keyword(s):  
Septic Shock ◽  
Retrospective Cohort ◽  
Primary Outcome ◽  
Standard Dose ◽  
Hemodynamic Response ◽  
Percentage Change ◽  
High Dose ◽  
Obese Patients ◽  
Improved Outcomes ◽  
Higher Doses

Background No clear association between standard vasopressin doses and body mass index exists, despite potential pharmacokinetic and pharmacodynamic variability among patients with septic shock. It is unknown if higher doses may alter hemodynamic response. Objective The purpose of this study was to evaluate the effect of vasopressin dose on hemodynamic response in obese patients with septic shock. Methods A single-center, retrospective cohort study was conducted in adult, obese patients with septic shock receiving catecholamine vasopressors and vasopressin. Patients were analyzed according to vasopressin dose received: standard dose (≤0.04 U/min) and high dose (>0.04 U/min). The primary outcome was percentage change in norepinephrine equivalent (NEQ) dose. Results A total of 182 patients were included in the analysis, with 136 in the standard-dose vasopressin group and 46 in the high-dose vasopressin group. There was no difference in percentage change in NEQ dose at 6 hours after standard- or high-dose vasopressin attainment (−28.6% vs −19.1%; P = 0.166). A greater increase in mean arterial pressure (MAP) at 6 hours was observed with receipt of high-dose vasopressin (23.3% vs 15.3%; P = 0.023). Duration of shock and length of stay were significantly longer in patients who received high-dose vasopressin, with no difference in in-hospital mortality. Conclusion and Relevance This represents the first analysis comparing standard and higher doses of vasopressin in obese patients with septic shock. Receipt of high-dose vasopressin was not associated with a difference in catecholamine requirement or improved outcomes. Further studies are warranted to provide guidance on the use of high-dose vasopressin in septic shock.

Evaluation of a Fixed-Dose Regimen of 4-Factor Prothrombin Complex Concentrate for Warfarin Reversal

2021 ◽  
pp. 106002802199214
Author(s):  
Clare McMahon ◽  
Joe Halfpap ◽  
Qianqian Zhao ◽  
Ana Bienvenida ◽  
Anne E. Rose
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Dose Regimen ◽  
Prothrombin Complex Concentrate ◽  
Primary Outcome ◽  
International Normalized Ratio ◽  
Fixed Dose ◽  
Optimal Dosing ◽  
Warfarin Reversal ◽  
Higher Doses

Background: Fixed-dose (FD) regimens of 4-factor prothrombin complex concentrate (4F-PCC) may be effective for the emergent reversal of warfarin; however, the optimal dosing is unknown. Our institution transitioned to a FD regimen of 1000 or 2000 units of 4F-PCC based on indication. Objective: The purpose of this study is to report our experience with FD 4F-PCC compared with a historical weight-based dosing cohort for warfarin reversal. Methods: A retrospective analysis was conducted for 3 groups: central nervous system (CNS) bleeds regardless of international normalized ratio (INR), non-CNS bleeds with an initial INR ≤6, and non-CNS bleeds with an initial INR ≥6.1. The primary outcome of the study was achievement of the target INR. Results: There were 54 patients with a CNS bleed, 153 with a non-CNS bleed and INR ≤6, and 19 with a non-CNS bleed and INR ≥6.1. In the CNS bleeding group, weight-based and FD achieved target INR 79.4% and 70% ( P = 0.52). In the INR ≥6.1 non-CNS bleeding group, weight-based and FD achieved target INR 100% and 70% ( P = 0.21). In the INR ≤6 non-CNS bleeding group, weight-based and FD achieved target INR 86.4% and 57.5% ( P = 0.0002). Conclusion and Relevance: An FD strategy of 2000 units for warfarin reversal for CNS bleeds or INR ≥6.1 was comparable to weight-based dosing. The FD strategy of 1000 units for INR ≤6 achieved target INR less often than weight-based dosing. Application of findings suggest that higher doses may be needed to achieve target INR.

scholarly journals Distribution and titres of rotavirus antibodies in different age groups

1977 ◽  
Vol 79 (3) ◽  
pp. 365-372 ◽  
Author(s):  
M. M. Elias
Keyword(s):  
Indirect Immunofluorescence ◽  
Acute Gastroenteritis ◽  
Neutralizing Antibodies ◽  
Complement Fixation ◽  
Age Groups ◽  
Newborn Infants ◽  
Older Age ◽  
Human Rotavirus ◽  
Hospital Patients

SUMMARYThree hundred and fifty-seven sera selected at random from hospital patients of all ages were examined for rotavirus antibodies using indirect immunofluorescence (FA) and complement fixation tests (CFT). Three hundred and fourteen of these were also tested for neutralizing antibodies to human rotavirus. Sera from patients admitted with a diagnosis of acute gastroenteritis were excluded from this survey.FA antibodies were found in newborn infants but fell to undetectable titres at 3 months. The highest titres were found in children between the ages of one and three years. In older age groups, the modal titre fell gradually with increasing age until, in sera from those above 70 years of age, FA antibodies were almost undetectable. The same pattern was observed with neutralizing antibodies. A high modal titre of CF antibodies was only found in sera from those aged one to three years.

Phase I Trial of Intravenous Administration of PV701, an Oncolytic Virus, in Patients With Advanced Solid Cancers

2002 ◽  
Vol 20 (9) ◽  
pp. 2251-2266 ◽  
Author(s):  
Andrew L. Pecora ◽  
Naiyer Rizvi ◽  
Gary I. Cohen ◽  
Neal J. Meropol ◽  
Daniel Sterman ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase I ◽  
Intravenous Administration ◽  
Single Agent ◽  
Progression Free Survival ◽  
Maximum Tolerated Dose ◽  
Repeat Dose ◽  
Tumor Cell Membrane ◽  
Dosing Regimens ◽  
Higher Doses

PURPOSE: PV701, a replication-competent strain of Newcastle disease virus, causes regression of tumor xenografts after intravenous administration. This phase I study was designed to define the maximum-tolerated dose (MTD) and safety of single and multiple intravenous doses of PV701 as a single agent in patients with cancer. PATIENTS AND METHODS: Seventy-nine patients with advanced solid cancers that were unresponsive to standard therapy were enrolled. Four PV701 intravenous dosing regimens were evaluated: (1) single dose: one dose every 28 days; (2) repeat dose: three doses in 1 week every 28 days; (3) desensitizing: one lower dose followed by two higher doses in 1 week every 28 days; and (4) two week: one lower dose followed by five higher doses over 2 weeks every 21 days. RESULTS: A 100-fold dose intensification was achieved over 195 cycles. A first-dose MTD of 12 × 109 plaque-forming units (PFU)/m2 was established for outpatient dosing. After an initial dose of 12 × 109 PFU/m2, patients tolerated an MTD for subsequent doses of 120 × 109 PFU/m2. The most common adverse events were flu-like symptoms that occurred principally after the first dose and were decreased in number and severity with each subsequent dose. Tumor site–specific adverse events and acute dosing reactions were also observed but not cumulative toxicity. Objective responses occurred at higher dose levels, and progression-free survival ranged from 4 to 31 months. Tumor tissue from one patient was obtained after 11 months of therapy and showed evidence of PV701 particles budding from the tumor cell membrane by electron microscopy and a pronounced lymphoplasmacytic infiltrate by histologic examination. CONCLUSION: PV701 warrants further study as a novel therapeutic agent for cancer patients.

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