scholarly journals Longitudinal Pharmacokinetic-Pharmacodynamic Biomarkers Correlate With Treatment Outcome in Drug-Sensitive Pulmonary Tuberculosis: A Population Pharmacokinetic-Pharmacodynamic Analysis

2020 ◽  
Vol 7 (7) ◽  
Author(s):  
Frank Kloprogge ◽  
Henry C Mwandumba ◽  
Gertrude Banda ◽  
Mercy Kamdolozi ◽  
Doris Shani ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Treatment Success ◽  
Area Under The Curve ◽  
Outcome Data ◽  
Pharmacokinetic Parameters ◽  
Population Pharmacokinetic ◽  
Antibiotic Exposure ◽  
Sputum Conversion ◽  
Demographic Covariates ◽  
Pharmacodynamic Biomarkers

Abstract Background This study aims to explore relationships between baseline demographic covariates, plasma antibiotic exposure, sputum bacillary load, and clinical outcome data to help improve future tuberculosis (TB) treatment response predictions. Methods Data were available from a longitudinal cohort study in Malawian drug-sensitive TB patients on standard therapy, including steady-state plasma antibiotic exposure (154 patients), sputum bacillary load (102 patients), final outcome (95 patients), and clinical details. Population pharmacokinetic and pharmacokinetic-pharmacodynamic models were developed in the software package NONMEM. Outcome data were analyzed using univariate logistic regression and Cox proportional hazard models in R, a free software for statistical computing. Results Higher isoniazid exposure correlated with increased bacillary killing in sputum (P < .01). Bacillary killing in sputum remained fast, with later progression to biphasic decline, in patients with higher rifampicin area under the curve (AUC)0-24 (P < .01). Serial sputum colony counting negativity at month 2 (P < .05), isoniazid CMAX (P < .05), isoniazid CMAX/minimum inhibitory concentration ([MIC] P < .01), and isoniazid AUC0-24/MIC (P < .01) correlated with treatment success but not with remaining free of TB. Slower bacillary killing (P < .05) and earlier progression to biphasic bacillary decline (P < .01) both correlate with treatment failure. Posttreatment recurrence only correlated with slower bacillary killing (P < .05). Conclusions Patterns of early bacillary clearance matter. Static measurements such as month 2 sputum conversion and pharmacokinetic parameters such as CMAX/MIC and AUC0-24/MIC were predictive of treatment failure, but modeling of quantitative longitudinal data was required to assess the risk of recurrence. Pooled individual patient data analyses from larger datasets are needed to confirm these findings.

scholarly journals Is the Recommended Once-Daily Dose of Lamivudine Optimal in West African HIV-Infected Children?

2010 ◽  
Vol 54 (8) ◽  
pp. 3280-3286 ◽  
Author(s):  
Naïm Bouazza ◽  
Déborah Hirt ◽  
Christophe Bardin ◽  
Serge Diagbouga ◽  
Boubacar Nacro ◽  
...  
Keyword(s):  
Body Weight ◽  
Area Under The Curve ◽  
Compartment Model ◽  
Individual Characteristics ◽  
Pharmacokinetic Parameters ◽  
Population Pharmacokinetic ◽  
Parameter Estimates ◽  
Ratio Test ◽  
Once Daily ◽  
Time Courses

ABSTRACT We aimed in this study to describe lamivudine concentration-time courses in treatment-naïve children after once-daily administration, to study the effects of body weight and age on lamivudine pharmacokinetics, and to simulate an optimized administration scheme. For this purpose, lamivudine concentrations were measured in 49 children after at least 2 weeks of didanosine-lamivudine-efavirenz treatment. A total of 148 plasma lamivudine concentrations were measured, and a population pharmacokinetic model was developed with NONMEM. The influence of individual characteristics was tested using a likelihood ratio test. Children were divided into two groups, according to their pharmacokinetic parameters, thanks to tree regression analysis. For each patient, the area under the curve was derived from estimated individual pharmacokinetic parameters. Different once-daily doses were simulated in each group, to obtain the same exposure in children as the mean effective exposure in adults (8.9 mg/liter·h). A two-compartment model in which the slope of distribution is assumed to be equal to the absorption rate constant adequately described the data. Parameter estimates were standardized for a mean standard body weight using an allometric model. Children were then divided into 2 groups according to body weight: CL/F was significantly higher in children weighing less than 17 kg (1.12 liters/h/kg) than in children over 17 kg (0.95 liters/h/kg; P = 0.01). The target mean AUC of 8.9 mg/liters·h was obtained with a 10-mg/kg once-daily lamivudine (3TC) dose for children below 17 kg; the recommended dose of 8 mg/kg seems to be sufficient in children weighing more than 17 kg. These assumptions should be prospectively confirmed.

scholarly journals Pharmacokinetics of Ganciclovir during Continuous Venovenous Hemodiafiltration in Critically Ill Patients

2013 ◽  
Vol 58 (1) ◽  
pp. 94-101 ◽  
Author(s):  
Thomas Horvatits ◽  
Reinhard Kitzberger ◽  
Andreas Drolz ◽  
Christian Zauner ◽  
Walter Jäger ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
High Performance ◽  
Area Under The Curve ◽  
Antiviral Agent ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Population Pharmacokinetic ◽  
Target Area ◽  
Continuous Venovenous Hemodiafiltration

ABSTRACTGanciclovir is an antiviral agent that is frequently used in critically ill patients with cytomegalovirus (CMV) infections. Continuous venovenous hemodiafiltration (CVVHDF) is a common extracorporeal renal replacement therapy in intensive care unit patients. The aim of this study was to investigate the pharmacokinetics of ganciclovir in anuric patients undergoing CVVHDF. Population pharmacokinetic analysis was performed for nine critically ill patients with proven or suspected CMV infection who were undergoing CVVHDF. All patients received a single dose of ganciclovir at 5 mg/kg of body weight intravenously. Serum and ultradiafiltrate concentrations were assessed by high-performance liquid chromatography, and these data were used for pharmacokinetic analysis. Mean peak and trough prefilter ganciclovir concentrations were 11.8 ± 3.5 mg/liter and 2.4 ± 0.7 mg/liter, respectively. The pharmacokinetic parameters elimination half-life (24.2 ± 7.6 h), volume of distribution (81.2 ± 38.3 liters), sieving coefficient (0.76 ± 0.1), total clearance (2.7 ± 1.2 liters/h), and clearance of CVVHDF (1.5 ± 0.2 liters/h) were determined. Based on population pharmacokinetic simulations with respect to a target area under the curve (AUC) of 50 mg · h/liter and a trough level of 2 mg/liter, a ganciclovir dose of 2.5 mg/kg once daily seems to be adequate for anuric critically ill patients during CVVHDF.

scholarly journals Vancomycin Treatment Failure in Children With Methicillin-Resistant Staphylococcus aureus Bacteremia

2019 ◽  
Vol 24 (4) ◽  
pp. 312-319 ◽  
Author(s):  
Rebecca B. Regen ◽  
Sarah S. Schuman ◽  
Rebecca F. Chhim ◽  
Sandra R. Arnold ◽  
Kelley R. Lee
Keyword(s):  
Staphylococcus Aureus ◽  
Treatment Failure ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Treatment Success ◽  
Area Under The Curve ◽  
Failure Criteria ◽  
Methicillin Resistant ◽  
Staphylococcus Aureus Bacteremia ◽  
Persistent Bacteremia ◽  
Vancomycin Treatment

OBJECTIVES Limited data exist regarding clinical outcomes of invasive methicillin-resistant Staphylococcus aureus (MRSA) infections in children treated with vancomycin. Treatment success in adults correlates best with an area under the curve/minimum inhibitory concentration (AUC24/MIC) ratio ≥400. It is unknown if this relationship is useful in children. METHODS Charts of children who received vancomycin ≥5 days for MRSA bacteremia with a steady state trough were reviewed. AUC24/MIC ratios were estimated using 2 different vancomycin clearance equations. Vancomycin treatment failure was defined as persistent bacteremia ≥7 days, recurrent bacteremia within 30 days, or 30-day mortality. RESULTS There were 67 bacteremia episodes in 65 patients. Nine (13.4%) met failure criteria: persistent bacteremia (n = 6), recurrent bacteremia (n = 2), 30-day mortality (n = 1). There were no differences between patients receiving <60 mg/kg/day and ≥60 mg/kg/day of vancomycin in median trough (11.9 versus 12.3 mg/L, p = 0.1). Troughs did not correlate well with AUC24/MIC ratios (R2 = 0.32 and 0.22). Patients receiving ≥60 mg/kg/day had greater probability of achieving ratios ≥400. There were no significant differences in median dose (p = 0.8), trough (p = 0.24), or AUC24/MIC ratios (p = 0.07 and p = 0.6) between patients with treatment success and failure. CONCLUSIONS Treatment failure was lower than previously reported in children. AUC24/MIC ratios ≥400 were frequently achieved but were not associated with treatment success, dose, or troughs. Prospective studies using standard definitions of vancomycin treatment failure are needed to understand treatment failure in children with MRSA bacteremia.

scholarly journals PK-DB: PharmacoKinetics DataBase for Individualized and Stratified Computational Modeling

2019 ◽  
Author(s):  
Jan Grzegorzewski ◽  
Janosch Brandhorst ◽  
Dimitra Eleftheriadou ◽  
Kathleen Green ◽  
Matthias König
Keyword(s):  
Computational Modeling ◽  
Computational Models ◽  
Smoking Status ◽  
Meta Analysis ◽  
Area Under The Curve ◽  
Pharmacokinetic Parameters ◽  
Population Pharmacokinetic ◽  
Special Focus ◽  
Biological Ontologies ◽  
Time Courses

ABSTRACTA multitude of pharmacokinetics studies have been published. However, due to the lack of an open database, pharmacokinetics data, as well as the corresponding meta-information, have been difficult to access. We present PK-DB (https://pk-db.com), an open database for pharmacokinetics information from clinical trials including pre-clinical research. PK-DB provides curated information on (i) characteristics of studied patient cohorts and subjects (e.g. age, bodyweight, smoking status); (ii) applied interventions (e.g. dosing, substance, route of application); (iii) measured pharmacokinetic time-courses; (iv) pharmacokinetic parameters (e.g. clearance, half-life, area under the curve). Key features are the representation of experimental errors, the normalization of measurement units, annotation of information to biological ontologies, calculation of pharmacokinetic parameters from concentration-time profiles, a workflow for collaborative data curation, strong validation rules on the data, computational access via a REST API as well as human access via a web interface. PK-DB enables meta-analysis based on data from multiple studies and data integration with computational models. A special focus lies on meta-data relevant for individualized and stratified computational modeling with methods like physiologically based pharmacokinetic (PBPK), pharmacokinetic/pharmacodynamic (PK/DB), or population pharmacokinetic (pop PK) modeling.

VHL protein (pVHL) and Src expression in metastatic RCC.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 457-457
Author(s):  
Kyle William Robinson ◽  
Yiyi Chen ◽  
Jennifer Podolak ◽  
Kerri Forquer ◽  
Megan Cook ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Treatment Success ◽  
Area Under The Curve ◽  
Predictive Ability ◽  
Metastatic Tumor ◽  
Roc Curve Analysis ◽  
Src Signaling ◽  
Vhl Protein ◽  
Tumor Expression ◽  
Metastatic Rcc

457 Background: Rational therapeutic strategies are lacking for RCC with intact pVHL expression. We recently demonstrated that Src signaling output was elevated in RCC cells expressing pVHL (Suwaki Sci Transl Med 2011). We sought to prospectively identify and clinically characterize RCC patients according to tumor expression of pVHL and Src using an immunohistochemical (IHC) assay, including the association of pVHL and Src expression with response to targeted therapies. Methods: Metastatic RCC patients with available archival tumor tissue provided written informed consent. Primary and metastatic tumors were evaluated by IHC staining using the following scale: 0: absent; 1: weak; 2: moderate-strong. We scored the percent of tumor cells staining at these intensities, giving a total possible score of 200. Association of pVHL and Src score was determined using Spearman correlation coefficient. Time to treatment failure (TTF) > 300 days was used to stratify patients as treatment success versus failure. Logistic regression was used to analyze whether there was an association between pVHL and Src staining and clinical outcome, and ROC curve analysis was used to find the predictive ability of pVHL and Src positivity. Results: 27 patients were consented, from which the nephrectomy specimens of 23 patients and 17 metastatic tumor samples were available. 22 patients had received systemic therapy (21 with VEGF TKI, 1 with mTOR-I). Expression of pVHL and Src were positively correlated (p<0.001). Expression of pVHL in primary tumor, but not Src, was associated with fewer treatment failure events (p=0.0384). Those who had TTF > 300 days had a mean pVHL score of 127.3, and Src of 134, while those with TTF < 300 days had mean pVHL of 57.5, and Src 89.5. Performing ROC analysis, the combination of pVHL and Src score displayed a higher area under the curve (c=0.8) in predicting treatment failure or success than pVHL or Src score alone. Conclusions: We have shown a correlation between pVHL and Src expression in tumors from a prospective population of RCC patients. Accrual continues to this study of a novel quantitative IHC profile that could identify patients for whom currently available therapies may not be effective or for whom a clinical trial of a Src inhibitor may be appropriate.

scholarly journals Clinical Profiles and Prediction of Treatment Failure in Patients with Tuberculosis

2020 ◽  
Author(s):  
Hyeon-Kyoung Koo ◽  
Jinsoo Min ◽  
Hyung Woo Kim ◽  
Joosun Lee ◽  
Ju Sang Kim ◽  
...  
Keyword(s):  
Risk Factors ◽  
Treatment Failure ◽  
Lung Disease ◽  
Treatment Success ◽  
Multivariable Analysis ◽  
Previous History ◽  
Area Under The Curve ◽  
Treatment Compliance ◽  
Poor Compliance ◽  
Cross Sectional

Abstract Background To improve the treatment outcomes for tuberculosis (TB) efforts to reduce treatment failure are necessary. The aim of our study was to describe the characteristics of subjects who had failed treatment of tuberculosis and identify the risk factors for treatment failure and poor compliance using national data.Methods A multicenter cross-sectional study was performed for tuberculosis subjects whose final outcome was reported as treatment failure during 2015–2017. The same number of subjects with treatment success during the same study period were randomly selected for comparison. Demographics, microbiological, radiographic, and clinical data were collected based on in-depth interviews by TB nurse specialists at all Public Private Mix (PPM) participating hospitals in South Korea.Results A total of 52 tuberculosis patients with treatment failure were enrolled. In a multivariable analysis, the presence of diabetes, previous history of tuberculosis, and cavity were identified as risk factors for treatment failure; and Medicaid support was a favorable factor for treatment success (area under the curve (AUC): 0.76). Age, diabetes, pre-existing lung disease, positive sputum acid-fast bacilli (AFB) smear result, and presence of multi-drug-resistant tuberculosis (MDR-TB) were significantly associated with presence of cavity. Younger age, and lower body mass index (BMI) were associated with poor compliance during treatment (AUC: 0.74).Conclusion To reduce treatment failure, careful evaluation for the presence of diabetes, underlying lung disease, cavity, results of sputum AFB smears, and socioeconomic status is needed. To enhance treatment compliance, more attention should be paid to younger patients with lower BMIs during follow-up.

scholarly journals PK-DB: pharmacokinetics database for individualized and stratified computational modeling

2020 ◽  
Vol 49 (D1) ◽  
pp. D1358-D1364
Author(s):  
Jan Grzegorzewski ◽  
Janosch Brandhorst ◽  
Kathleen Green ◽  
Dimitra Eleftheriadou ◽  
Yannick Duport ◽  
...  
Keyword(s):  
Computational Modeling ◽  
Computational Models ◽  
Smoking Status ◽  
Meta Analysis ◽  
Area Under The Curve ◽  
Pharmacokinetic Parameters ◽  
Population Pharmacokinetic ◽  
Special Focus ◽  
Biological Ontologies ◽  
Time Courses

Abstract A multitude of pharmacokinetics studies have been published. However, due to the lack of an open database, pharmacokinetics data, as well as the corresponding meta-information, have been difficult to access. We present PK-DB (https://pk-db.com), an open database for pharmacokinetics information from clinical trials. PK-DB provides curated information on (i) characteristics of studied patient cohorts and subjects (e.g. age, bodyweight, smoking status, genetic variants); (ii) applied interventions (e.g. dosing, substance, route of application); (iii) pharmacokinetic parameters (e.g. clearance, half-life, area under the curve) and (iv) measured pharmacokinetic time-courses. Key features are the representation of experimental errors, the normalization of measurement units, annotation of information to biological ontologies, calculation of pharmacokinetic parameters from concentration-time profiles, a workflow for collaborative data curation, strong validation rules on the data, computational access via a REST API as well as human access via a web interface. PK-DB enables meta-analysis based on data from multiple studies and data integration with computational models. A special focus lies on meta-data relevant for individualized and stratified computational modeling with methods like physiologically based pharmacokinetic (PBPK), pharmacokinetic/pharmacodynamic (PK/PD), or population pharmacokinetic (pop PK) modeling.

EUROPEAN PAEDIATRIC ONCOLOGY OFF-PATENT MEDICINES CONSORTIUM (EPOC): A PHARMACOKINETIC STUDY OF DOXORUBICIN IN CHILDREN WITH CANCER

2015 ◽  
Vol 101 (1) ◽  
pp. e1.6-e1
Author(s):  
Miriam Krischke ◽  
Alan V Boddy ◽  
Georg Hempel ◽  
Swantje Völler ◽  
Nicolas André ◽  
...  
Keyword(s):  
Pharmacokinetic Study ◽  
Cardiac Troponin ◽  
Troponin T ◽  
Paediatric Oncology ◽  
Patient Acceptance ◽  
Pharmacokinetic Parameters ◽  
Blood Levels ◽  
Population Pharmacokinetic ◽  
Older Children ◽  
Treatment Regimens

BackgroundDoxorubicin is a key component of a number of treatment regimens used in paediatric oncology. The pharmacology data on which current dosing regimens are based are very limited.MethodsWe conducted a multicentre, multinational pharmacokinetic study investigating age-dependency in the clearance of doxorubicin in children with solid tumours and leukaemia. Blood samples for measurement of doxorubicin and its metabolite doxorubicinol were collected after 2 administrations, with 5 samples collected in children 3 yrs. A population pharmacokinetic approach was used for analysis, including pharmacogenetic covariates. NT-proBNP and cardiac troponin T were measured to evaluate their role as early indicators of cardiotoxicity.Results101 children could be recruited including 27 patients less than 3 years and among those 5 infants younger than 1 year. Overall, the patient acceptance of the trial was very good.Age dependence of doxorubicin clearance was demonstrated, with children less than 3 years having a lower clearance (21.1±5.8 l/h/m2) than older children (26.6±6.7 l/h/m2) (p=0.0004), after correcting for body weight. Pharmacogenetic variants, including those in transporters and drug metabolizing enzymes, had little influence on pharmacokinetic parameters.Natriuretic peptides plasma levels increased significantly shortly after doxorubicin administration, whereas cardiac troponin levels increased only with the administered cumulative anthracycline dose. Only limited correlation could be observed between their blood levels and doxorubicin pharmacokinetics.ConclusionThe paediatric need concerning missing PK-data could be addressed with limited burden for the patients. Empirically used dose adaptations for infants were found to be justified based on our PK analyses.

POPULATION PHARMACOKINETICS AND DOSING OPTIMIZATION OF TEICOPLANIN IN CHILDREN WITH MALIGNANT HAEMATOLOGICAL DISEASE

2015 ◽  
Vol 101 (1) ◽  
pp. e1.41-e1
Author(s):  
Wei Zhao ◽  
Daolun Zhang ◽  
Thomas Storme ◽  
André Baruchel ◽  
Xavier Declèves ◽  
...  
Keyword(s):  
Population Pharmacokinetics ◽  
Haematological Malignancy ◽  
External Validation ◽  
Predictive Performance ◽  
Paediatric Population ◽  
Pharmacokinetic Parameters ◽  
Therapeutic Drug ◽  
Population Pharmacokinetic ◽  
High Risk Population ◽  
Dosing Regimen

BackgroundChildren with haematological malignancy represent an identified subgroup of the paediatric population with specific pharmacokinetic parameters. In these patients, inadequate empirical antibacterial therapy may result in infection-related morbidity and increased mortality, making optimization of the dosing regimen essential. As paediatric data are limited, our aim was to evaluate the population pharmacokinetics of teicoplanin in order to define the appropriate dosing regimen in this high-risk population.MethodsThe current dose of teicoplanin was evaluated in children with haematological malignancy. Population pharmacokinetics of teicoplanin was analysed using NONMEM software. The dosing regimen was optimised based on the final model.ResultsEighty-five children (age range: 0.5 to 16.9 years) were included. Therapeutic drug monitoring and opportunistic samples (n=143) were available for analysis. With the current recommended dose of 10 mg/kg/day, 41 children (48%) had sub-therapeutic steady-state trough concentrations (Css,min<10 mg/liter). A two-compartment pharmacokinetic model with first-order elimination was developed. Systematic covariate analysis identified that bodyweight (size) and creatinine clearance significantly influenced teicoplanin clearance. The model was validated internally. Its predictive performance was further confirmed in an external validation. In order to reach the target AUC of 750 mg·h/L, 18 mg/kg was required for infants, 14 mg/kg for children and 12 mg/kg for adolescents. A patient-tailored dose regimen was further developed and reduced variability in AUC and Css,min values compared to the mg/kg-basis dose, making the modelling approach an important tool for dosing individualization.ConclusionsThis first population pharmacokinetic study of teicoplanin in children with haematological malignancy provided evidence-based support to individualize teicoplanin therapy in this vulnerable population.

scholarly journals 1319. Pharmacokinetics of Ceftolozane/Tazobactam in Patients with Burns

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S670-S671
Author(s):  
Ronald G Hall ◽  
Jotam Pasipanodya ◽  
William C Putnam ◽  
John Griswold ◽  
Sharmila Dissanaike ◽  
...  
Keyword(s):  
Human Plasma ◽  
Kidney Injury ◽  
Compartment Model ◽  
Pharmacokinetic Parameters ◽  
Therapeutic Drug ◽  
Population Pharmacokinetic ◽  
Parameter Estimates ◽  
Population Parameter ◽  
Full Thickness ◽  
Severe Burns

Abstract Background Antimicrobial dosing in moderate/severe burns patients is complicated due to the potential unpredictable hyperdynamic pathophysiologic states including 1) hypoproteinemia, 2) acute kidney injury and 3) onset of septicemia. Therefore, distribution assumptions about the population pharmacokinetic (PopPK) profiles of either endogenous or xenobiotic pharmacophores in this patient population can lead to biased parameter estimates. In order to prevent potential bias an agnostic nonparametric adaptive grid approach to describe ceftolozane/tazobactam (C/T) PopPK profiles in patients with partial- and full-thickness burns was employed. Methods A human clinical PK study in burn patients was conducted using the standard approved dose of C/T (2 grams/1 gram). A single intravenous dose was administered over 60 minutes. Whole blood was obtained pre-dose and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, and 24 hours following the start of infusion. LC-MS/MS bioanalytical methods were developed, validated and employed to determine C/T concentrations in human plasma. PopPK were modeled using Pmetrics package for R. One-, two- and three-compartment models were examined and compared. The influence of several parameters, including %body surface area burns, creatinine clearance (CrCL), weight, albumin and age were tested. Results The bioanalytical method for determination of C/T in human plasma met all recommended criteria of the LC-MS/MS. Five males and one female (ages 24 to 66 years), contributed 148 plasma PK samples. The female had 35% partial-thickness burns. The males had full-thickness burns ranging from 27 to 66%. The median CrCL was 104 mL/min (range 73-148 mL/min). Two-compartment model with absorption (Ka) from compartment 1 to 2 and elimination from compartment 2 (Ke), with nonlinear interactions between C/T elimination and CrCL best described the data. Figure A show that bias was minimal. Importantly, both drugs exhibited marked variability for both volume and elimination (Table), since volume was bimodally distributed (Figure B). A) Observation-versus-Prediction; B) Estimated Ke, V and Ka population parameter densities Summary of pharmacokinetic parameters Conclusion C/T exhibited high variability surpassing that observed with severe infections, suggesting that dose adjustment and/or may be therapeutic drug monitoring may be needed to balance target attainment from dose-related toxicities. Disclosures Ronald G. Hall, II, PharmD, MSCS, Medical Titan Group (Grant/Research Support)Merck (Research Grant or Support)

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