scholarly journals Methylprednisolone Plasma Concentrations During Cardiac Surgery With Cardiopulmonary Bypass in Pediatric Patients

2021 ◽  
Vol 8 ◽  
Author(s):  
Annewil van Saet ◽  
Gerdien A. Zeilmaker-Roest ◽  
Kevin M. Veen ◽  
Saskia N. de Wildt ◽  
Fritz Sorgel ◽  
...  
Keyword(s):  
Cardiac Surgery ◽  
Cardiopulmonary Bypass ◽  
Pediatric Patients ◽  
Plasma Concentrations ◽  
Volume Of Distribution ◽  
Steep Slope ◽  
Time Curve ◽  
Linear Mixed Effects ◽  
Mixed Effects Modeling ◽  
Liquid Chromatography Tandem Mass

Introduction: To our knowledge, methylprednisolone pharmacokinetics and plasma concentrations have not been comprehensively investigated in children with congenital heart disease undergoing cardiac surgery with cardiopulmonary bypass. It is unknown whether there is a significant influence of cardiopulmonary bypass on the plasma concentrations of methylprednisolone and whether this may be an explanation for the limited reported efficacy of steroid administration in cardiac surgery with cardiopulmonary bypass.Methods: The study was registered in the Dutch Trial Register (NTR3579; https://www.trialregister.nl/trial/3428). Methylprednisolone 30 mg/kg was administered as an intravenous bolus after induction of anesthesia. Methylprednisolone concentration was measured with liquid chromatography tandem mass spectrometry and analyzed using linear mixed-effects modeling.Results: Thirty-nine patients were included in the study, of which three were excluded. There was an acute decrease in observed methylprednisolone plasma concentration on initiation of cardiopulmonary bypass (median = 26.8%, range = 13.9–48.14%, p < 0.001). We found a lower intercept (p = 0.02), as well as a less steep slope of the model predicted methylprednisolone concentration vs. time curve for neonates (p = 0.048). A lower intercept (p = 0.01) and a less steep slope (p = 0.0024) if the volume of cell saver blood processed was larger than 91 ml/kg were also found.Discussion: We report similar methylprednisolone plasma concentrations as earlier studies performed in children undergoing cardiopulmonary bypass, and we confirmed the large interindividual variability in achieved methylprednisolone plasma concentrations with weight-based methylprednisolone administration. A larger volume of distribution and a lower clearance of methylprednisolone for neonates were suggested. The half-life of methylprednisolone in our study was calculated to be longer than 6 h for neonates, 4.7 h for infants, 3.6 h for preschool children and 4.7 h for school children. The possible influence of treatment of pulmonary hypertension with sildenafil and temperature needs to be investigated further.

scholarly journals Tigecycline Does Not Prolong Corrected QT Intervals in Healthy Subjects

2013 ◽  
Vol 57 (4) ◽  
pp. 1895-1901 ◽  
Author(s):  
Joan M. Korth-Bradley ◽  
Paul C. McGovern ◽  
Joanne Salageanu ◽  
Kyle Matschke ◽  
Anna Plotka ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Volume Of Distribution ◽  
Mixed Effects ◽  
Pharmacokinetic Parameters ◽  
Qtc Interval ◽  
Open Label ◽  
Time Curve ◽  
Linear Mixed Effects ◽  
Mixed Effects Modeling ◽  
Qt Intervals

ABSTRACTWe evaluated the effect of tigecycline (50-mg and 200-mg doses) on corrected QT (QTc) intervals and assessed safety and tolerability in a randomized, placebo-controlled, four-period crossover study of 48 (44 male) healthy volunteers aged 22 to 53 years. Fed subjects received tigecycline (50 mg or 200 mg) or placebo in a blinded fashion or an open-label oral dose of moxifloxacin (400 mg) after 1 liter of intravenous fluid. Serial electrocardiograms were recorded before, and for 96 h after, dosing. Blood samples for tigecycline pharmacokinetics were collected after each recording. QTc intervals were corrected using Fridericia's correction (QTcF). Pharmacokinetic parameters were calculated using noncompartmental methods with potential relationships examined using linear mixed-effects modeling. Adverse events were recorded. The upper limits of the 90% confidence interval for the mean difference between both tigecycline doses and placebo for all time-matched QTcF interval changes from baseline were <5 ms. The tigecycline concentrations initially declined rapidly and then more slowly. In the group given 50 mg of tigecycline, the pharmacokinetic parameters and means were as follows: maximum concentration of drug in serum (Cmax), 432 ng/ml; area under the concentration-time curve from time zero extrapolated to infinity (AUC0–∞), 2,366 ng · h/ml; clearance (CL), 21.1 liters/h; volume of distribution at steady state (Vss), 610 liters; and terminal half-life (t1/2), 22.1 h. Proportional or similar values were found for the group given 200 mg of tigecycline. Linear mixed-effects modeling failed to show an effect on QTcF values by tigecycline concentrations (P= 0.755). Tigecycline does not prolong the QTc interval in healthy subjects. This study has been registered at ClinicalTrials.gov under registration no. NCT01287793.

Clinical Pharmacology and Efficacy of Ticarcillin in Infants and Children

PEDIATRICS ◽  
1978 ◽  
Vol 61 (6) ◽  
pp. 858-863 ◽  
Author(s):  
John D. Nelson ◽  
Helen Kusmiesz ◽  
Sharon Shelton ◽  
Edythe Woodman
Keyword(s):  
Pediatric Patients ◽  
Plasma Concentrations ◽  
Volume Of Distribution ◽  
Older Children ◽  
Efficacy Data ◽  
Suspected Sepsis ◽  
Suitable Alternative ◽  
Young Infants ◽  
Limited Efficacy ◽  
Pseudomonas Infection

Ticarcillin was evaluated in 82 neonates and young infants with suspected sepsis and in 16 older children with chronic Pseudomonas infection of the mastoids. The infants also received kanamycin. Individual ticarcillin doses of 75 or 100 mg/kg were given every four, six, or eight hours by intramuscular injection or by a 30-minute intravenous infusion. Mean plasma concentrations one hour after a dose were from 125 to 189 µg/ml, depending on dosage, age, and maturity. Mean plasma half-lives were approximately 5 hours in the first week of life, 2 hours in infants from 1 to 8 weeks, and 0.9 hours in older children. Volume of distribution was approximately twice as great in infants as in children, and plasma clearance rates correlated inversely with age. Limited efficacy data suggest that ticarcillin is a suitable alternative to ampicillin or carbenicillin, when given concurrently with an aminoglycoside, for newborn infections. When given for several days before mastoidectomy and tympanoplasty, ticarcillin sterilized the mastoids in the majority of patients. A new dosage schedule for ticarcillin in pediatric patients is proposed.

scholarly journals Single-Ascending-Dose Pharmacokinetics and Safety of the Novel Broad-Spectrum Antifungal Triazole BAL4815 after Intravenous Infusions (50, 100, and 200 Milligrams) and Oral Administrations (100, 200, and 400 Milligrams) of Its Prodrug, BAL8557, in Healthy Volunteers

2006 ◽  
Vol 50 (1) ◽  
pp. 279-285 ◽  
Author(s):  
Anne Schmitt-Hoffmann ◽  
Brigitte Roos ◽  
Markus Heep ◽  
Michael Schleimer ◽  
Erhard Weidekamm ◽  
...  
Keyword(s):  
Broad Spectrum ◽  
Plasma Concentrations ◽  
Pathogenic Fungi ◽  
Volume Of Distribution ◽  
The Body ◽  
Water Soluble ◽  
Maximum Plasma ◽  
Serious Adverse Events ◽  
Time Curve ◽  
To Receive

ABSTRACT BAL8557 is the water-soluble prodrug of a novel antifungal triazole, BAL4815. BAL4815 is active against a broad spectrum of major opportunistic and pathogenic fungi, including strains that are resistant to other azoles. Cohorts of healthy male subjects received single-ascending oral (p.o.) doses of BAL8557 that were equivalent to 100, 200, or 400 mg of BAL4815 or single-ascending, 1-h constant-rate intravenous (i.v.) infusions of BAL8557 which were equivalent to 50, 100, or 200 mg of BAL4815. In each cohort, six subjects were randomly assigned to receive active drug and two subjects were assigned to receive the placebo. All doses were well tolerated, and no severe or serious adverse events occurred. Maximum plasma concentrations of BAL4815 were observed 1.5 to 3 h after p.o. drug intake or at the end of the 1-h infusion. After both routes of administration, values for maximum drug concentration observed in plasma and area under the concentration-time curve increased slightly more than proportionally to the administered dose. Mean elimination half-lives were particularly long (56 to 77 h after p.o. administration and 76 to 104 h after i.v. administration). The volume of distribution was large (155 to 292 liters after p.o. administration and 304 to 494 liters after i.v. administration) and systemic clearance was low (1.9 to 2.8 liter/h after p.o. administration and 2.8 to 5.0 liter/h after i.v. administration). Urinary recovery of BAL4815 was less than 0.4% of the infused dose. Based on the exposure data, oral bioavailability of BAL4815 is assumed to be very high. The pharmacokinetics of BAL4815 are well suited to maintaining concentrations of BAL4815 for a long period of time in the body and to enabling an effective treatment of systemic mycoses.

scholarly journals Pharmacokinetics of Daptomycin in Critically Ill Pediatric Patients

2018 ◽  
Vol 62 (6) ◽  
Author(s):  
Charalampos Antachopoulos ◽  
Stavroula Ilia ◽  
Paschalis Kadiltzoglou ◽  
Eirini Baira ◽  
Aristides Dokoumetzidis ◽  
...  
Keyword(s):  
Critically Ill ◽  
Drug Exposure ◽  
Pediatric Patients ◽  
Plasma Concentrations ◽  
Therapeutic Drug ◽  
Burn Patients ◽  
Time Curve ◽  
Once Daily ◽  
Concentration Time ◽  
Optimal Drug

ABSTRACT The pharmacokinetics of daptomycin (10 mg/kg once daily) was studied in 4 critically ill pediatric patients aged 8 to 14 yrs. The area under the concentration-time curve from time zero to infinity (AUC 0–∞ ) of plasma concentrations on day 1 ranged between 123.8 to 663.9 μg · h/ml, with lower values observed in septic and burn patients; clearance ranged from 15.1 to 80.7 ml/h/kg. Higher-than-recommended doses of daptomycin may be needed in septic children to ensure optimal drug exposure. Interpatient variability may suggest a role for therapeutic drug monitoring.

scholarly journals Clinical Validation of the Analysis of Fluconazole in Oral Fluid in Hospitalized Children

2014 ◽  
Vol 58 (11) ◽  
pp. 6742-6746 ◽  
Author(s):  
Kim C. M. van der Elst ◽  
Manouche van Alst ◽  
Marjolijn N. Lub-de Hooge ◽  
Kai van Hateren ◽  
Jos G. W. Kosterink ◽  
...  
Keyword(s):  
Oral Fluid ◽  
Drug Exposure ◽  
Pediatric Patients ◽  
Pearson Correlation ◽  
Volume Of Distribution ◽  
Therapeutic Drug ◽  
Pearson Correlation Test ◽  
Liquid Chromatography Tandem Mass ◽  
Paired Serum ◽  
At Home

ABSTRACTFluconazole is a first-line antifungal agent for the treatment and prophylaxis of invasive candidiasis in pediatric patients. Pediatric patients are at risk of suboptimal drug exposure, due to developmental changes in gastrointestinal and renal function, metabolic capacity, and volume of distribution. Therapeutic drug monitoring (TDM) can therefore be useful to prevent underexposure of fluconazole in children and infants. Children, however, often fear needles and can have difficult vascular access. The purpose of this study was to develop and clinically validate a method of analysis to determine fluconazole in oral fluid in pediatric patients. Twenty-one paired serum and oral fluid samples were obtained from 19 patients and were analyzed using a validated liquid chromatography-tandem mass spectrometry (LC–MS-MS) method after cross-validation between serum and oral fluid. The results were within accepted ranges for accuracy and precision, and samples were stable at room temperature for at least 17 days. A Pearson correlation test for the fluconazole concentrations in serum and oral fluid showed a correlation coefficient of 0.960 (P< 0.01). The mean oral fluid-to-serum concentration ratio was 0.99 (95% confidence interval [CI], 0.88 to 1.10) with Bland-Altman analysis. In conclusion, an oral fluid method of analysis was successfully developed and clinically validated for fluconazole in pediatric patients and can be a noninvasive, painless alternative to perform TDM of fluconazole when blood sampling is not possible or desirable. When patients receive prolonged courses of antifungal treatment and use fluconazole at home, this method of analysis can extend the possibilities of TDM for patients at home.

scholarly journals 83 The predictive role of neutrophil-to-lymphocyte ratio in post-operative cardiopulmonary bypass surgery

2021 ◽  
Vol 23 (Supplement_G) ◽  
Author(s):  
Valentina Bucciarelli ◽  
Francesco Bianco ◽  
Annaclara Blasi ◽  
Martina Primavera ◽  
Baldinelli Alessandra ◽  
...  
Keyword(s):  
Cardiac Surgery ◽  
Cardiopulmonary Bypass ◽  
Pediatric Patients ◽  
Septal Defect ◽  
Left Ventricular ◽  
Conduction System ◽  
Neutrophil To Lymphocyte Ratio ◽  
Lymphocyte Ratio ◽  
Predictive Role

Abstract Aims Postoperative arrhythmias (POA) are a common complication after cardiac surgical repairs for congenital heart disease (CHD), representing a substantial source of morbidity, mortality, and prolonged total in-hospital stay, with an incidence of 7.5–48% in postoperative pediatric cardiac patients. The etiology is multifactorial, and it has been related to the direct surgical manipulation of the cardiac conduction system, to the local tissue inflammation in the myocardium adjacent to the conduction system and to the arrhythmogenic effects of cardiopulmonary bypass (CPB), inotropes, and electrolyte disturbances. Recently, the prognostic role of neutrophil-to-lymphocyte ratio (NLR), a novel inflammation marker, has been evaluated in pediatric patients after CPB surgery. To evaluate the predictive role of NLR in POA in a population of pediatric CHD patients after CPB. Methods and results We retrospectively collected perioperative clinical and laboratory data of 146 patients (age 8.27 ± 10.79 years; male gender: 60.8%) consecutively admitted to the cardiac surgery intensive care unit (ICU) of our institute after elective cardiac surgery with CPB in 2018. We grouped and analyzed our population over NLR tertiles evaluated at 24 h from CPB and types of POA: supraventricular (SVT) and junctional (JET). The prognostic value of NLR and its association with POA was analyzed. Diagnoses of 146 patients included atrial septal defect (n = 36), ventricular septal defect (n = 20), pulmonary atresia/stenosis (n = 10), tetralogy of Fallot (n = 20), endocardial cushion defect (n = 8), left ventricular outflow tract obstruction (n = 14), anomalous origin of coronary artery (n = 6), complex CHD (n = 13), interrupted/hypoplastic aortic arch (n = 12), anomalous pulmonary venous return (n = 3). The mean CPB time was 121.6 ± 84.6 min. The median ICU hospitalization was 48 h [Q1, Q3: 24, 96]. Twelve patients experienced POA: 6 SVT and 6 JET. The frequency of POA incremented over NLR-tertiles (P-Trend 0.017), while SVT onset was associated with higher values of NLR and C-reactive protein (P = 0.034 and P = 0.011, respectively). Patients in the second and third tertiles of NLR had a prolonged hospitalization (log-rank, P = 0.029), especially when associated with POA (log-rank, P = 0.012). At the multivariable analysis, higher age and NLR values were independently associated with SVT [OR per year 1.22; 95% CI (1.02, 1.25), P = 0.043 and OR per point 1.91; 95% CI (1.29, 2.82), P = 0.012, respectively], but not with JET. Conclusions 24-h post-CPB NLR can predict postoperative SVT in a population of pediatric CHD patients. Our data suggest that the NLR could be a useful, easy-to-obtain marker for postoperative outcome in pediatric patients who had undergone elective CPB.

scholarly journals Pharmacokinetic herb-drug interactions between Aidi injection and Doxorubicin in rats with diethylnitrosamine-induced hepatocellular carcinoma

2020 ◽  
Author(s):  
Yuan Lu ◽  
Jie Pan ◽  
Xiaoqing Zhu ◽  
Shuai Zhang ◽  
Liu Chunhua ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Drug Interactions ◽  
Plasma Concentrations ◽  
Ultra Performance Liquid Chromatography ◽  
Limited Information ◽  
Time Curve ◽  
Anti Cancer ◽  
Liquid Chromatography Tandem Mass ◽  
Aidi Injection ◽  
Reduced Toxicity

Abstract Background: Aidi Injection (ADI), a Chinese herbal preparation with anti-cancer activity, is used for the treatment of hepatocellular carcinoma (HCC). Several clinical studies have shown that co-administration of ADI with doxorubicin (DOX) is associated with reduced toxicity of chemotherapy, enhanced clinical efficacy and improved quality of life for patients. However, limited information is available about the herb-drug interactions between ADI and DOX. The study aimed to investigate the pharmacokinetic mechanism of herb-drug interactions between ADI and DOX in a rat model of HCC. Methods: Experimental HCC was induced in rats by oral administration of diethylnitrosamine. The HCC rats were pretreated with ADI (10 mL/kg, intraperitoneal injection) for 14 consecutive days prior to administration of DOX (7 mg/kg, intravenous injection) to investigate pharmacokinetic interactions. Plasma concentrations of DOX and its major metabolite, doxorubicinol (DOXol), were determined using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Results: Preadministration of ADI significantly altered the pharmacokinetics of DOX in HCC rats, leading to increased plasma concentrations of both DOX and DOXol. The area under the plasma drug concentration-time curve (AUCs) of DOX and DOXol in rats pretreated with ADI were 3.79-fold and 2.92-fold higher, respectively, than those in control rats that did not receive ADI. Conclusions: Increased levels of DOX and DOXol were found in the plasma of HCC rats pretreated with ADI.

Dose escalation of cyclophosphamide in patients with breast cancer: consequences for pharmacokinetics and metabolism.

1997 ◽  
Vol 15 (5) ◽  
pp. 1885-1896 ◽  
Author(s):  
D Busse ◽  
F W Busch ◽  
F Bohnenstengel ◽  
M Eichelbaum ◽  
P Fischer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dose Escalation ◽  
High Performance ◽  
Plasma Concentrations ◽  
Volume Of Distribution ◽  
High Dose ◽  
31P Nmr Spectroscopy ◽  
Metabolic Clearance ◽  
Time Curve ◽  
Relative Contribution

PURPOSE The alkylating anticancer agent cyclophosphamide (CP) is a prodrug that undergoes a complex metabolism in humans producing both active and inactive metabolites. In parallel, unchanged CP is excreted via the kidneys. The aim of this study was to investigate the influence of dose escalation on CP pharmacokinetics and relative contribution of activating and inactivating elimination pathways. PATIENTS AND METHODS Pharmacokinetics of CP were assessed in 12 patients with high-risk primary breast cancer who received an adjuvant chemotherapy regimen that included four courses of conventional-dose CP (500 mg/m2 over 1 hour every 3 weeks) followed by one final course of high-dose CP (100 mg/kg over 1 hour). Plasma concentrations of CP were analyzed by high-performance liquid chromatography (HPLC), 24-hour urinary concentrations of CP, and its inactive metabolites (carboxyphosphamide, dechloroethylcyclophosphamide [dechlorethylCP], ketocyclophosphamide [ketoCP]) were determined by 31-phosphorus-nuclear magnetic resonance (31P-NMR)-spectroscopy. RESULTS There was no difference in dose-corrected area under the concentration-time curve (AUC) (216 v 223 [mumol.h/[mL.g]), elimination half-life (4.8 v 4.8 hours), systemic clearance (79 v 77 mL/min) and volume of distribution (0.49 v 0.45 L/kg) of CP between conventional- and high-dose therapy, respectively. However, during high-dose chemotherapy, we observed a significant increase in the renal clearance of CP (15 v 23 mL/min; P < .01) and in the formation clearance of carboxyphosphamide (7 v 12 mL/min; P < .05) and dechloroethylCP (3.2 v 4.2 mL/min; P < .05), whereas metabolic clearance to ketoCP remained unchanged (1.3 v 1.2 mL/min). Consequently, metabolic clearance to the remaining (reactive) metabolites decreased from 52 to 38 mL/min (P < .001). The relative contribution of the different elimination pathways to overall clearance of CP demonstrated wide interindividual variability. CONCLUSION Overall pharmacokinetics of CP are apparently not affected during eightfold dose escalation. However, there is a shift in the relative contribution of different clearances to systemic CP clearance in favor of inactivating elimination pathways, thereby indicating saturation of bioactivating enzymes during dose escalation. Besides individual enzyme capacity, hydration and concomitant medication with dexamethasone modulated CP disposition.

scholarly journals Pharmacokinetics, urinary excretion and plasma protein binding of ofloxacin in water buffalo calves (Bubalus bubalis)

2013 ◽  
Vol 84 (1) ◽  
Author(s):  
Ajay K. Ola ◽  
Harpal S. Sandhu ◽  
Vinod K. Dumka ◽  
Bibhuti Ranjan
Keyword(s):  
Urinary Excretion ◽  
Half Life ◽  
High Performance ◽  
Water Buffalo ◽  
Plasma Concentrations ◽  
Pharmacokinetic Profile ◽  
Volume Of Distribution ◽  
Peripheral Compartment ◽  
Buffalo Calves ◽  
Time Curve

Pharmacokinetics and urinary excretion of an intravenous dose of 5 mg.kg–1 ofloxacin were investigated in water buffalo calves. Plasma concentrations of ofloxacin were determined by high-performance liquid chromatography. Ofloxacin was rapidly distributed from the central to the peripheral compartment as evidenced by a short distribution half-life (0.09 h ± 0.003 h) and high K12 (4.7 h–1 ± 0.1 h–1), and was detected in plasma for 8 h. The large volume of distribution (2.48 L.kg–1 ± 0.18 L.kg–1) obtained in this study indicated high distribution of ofloxacin in water buffalo calves. The elimination half-life, the area under the plasma drug concentration–time curve and total body clearance were 2.11 h ± 0.13 h, 6.20 µg.mL—1 ± 0.23 µg.mL—1.h and 0.81 mL.kg–1.h–1 ± 0.03 mL.kg–1.h–1, respectively. About 18.7% of administered drug was bound to plasma proteins and approximately 32.5% of the administered dose was recovered in urine within 48 h. The results of the study indicated a favourable pharmacokinetic profile of ofloxacin in water buffalo calves, which suggests that ofloxacin may be effective against urinary pathogens in this species.

scholarly journals Differences in the Pharmacokinetics of Gentamicin between Oncology and Nononcology Pediatric Patients

2019 ◽  
Vol 64 (2) ◽  
Author(s):  
C. C. Llanos-Paez ◽  
C. E. Staatz ◽  
R. Lawson ◽  
S. Hennig
Keyword(s):  
Fat Mass ◽  
Pediatric Patients ◽  
Drug Disposition ◽  
Therapeutic Index ◽  
Volume Of Distribution ◽  
Population Pharmacokinetic ◽  
Time Curve ◽  
Exposure Target ◽  
Low Exposure ◽  
The Impact

ABSTRACT Dosing gentamicin in pediatric patients can be difficult due to its narrow therapeutic index. A significantly higher percentage of fat mass has been observed in children receiving oncology treatment than in those who are not. Differences in the pharmacokinetics of gentamicin between oncology and nononcology pediatric patients and individual dosage requirements were evaluated in this study, using normal fat mass (NFM) as a body size descriptor. Data from 423 oncology and 115 nononcology patients were analyzed. Differences in drug disposition were observed between the oncology and nononcology patients, with oncology patients having a 15% lower central volume of distribution and 32% lower intercompartmental clearance. Simulations based on the population pharmacokinetic model demonstrated low exposure target attainment in all individuals at the current clinical recommended starting dose of 7.5 mg/kg of body weight once daily, with 57.4% of oncology and 35.7% of nononcology subjects achieving a peak concentration (Cmax) of ≥25 mg/liter and 64.3% of oncology and 65.6% of nononcology subjects achieving an area under the concentration-time curve at 24 h postdose (AUC24) of ≥70 mg · h/liter after the first dose. Based on simulations, the extent of the impact of differences in drug disposition between the two cohorts appeared to be dependent on the exposure target under examination. Greater differences in achieving a Cmax target of >25 mg/liter than an AUC24 target of ≥70 mg · h/liter between the cohorts was observed. Further investigation into whether differences in the pharmacokinetics of gentamicin between oncology and nononcology patients are a consequence of changes in body composition is required.

Sign in / Sign up

Export Citation Format

Share Document