scholarly journals The Pharmacokinetic Profile and Bioavailability of Enteral N-Acetylcysteine in Intensive Care Unit

Medicina ◽  
2021 ◽  
Vol 57 (11) ◽  
pp. 1218
Author(s):  
Kersti Teder ◽  
Liivi Maddison ◽  
Hiie Soeorg ◽  
Andres Meos ◽  
Juri Karjagin
Keyword(s):  
Intensive Care ◽  
Brain Injury ◽  
Healthy Volunteers ◽  
Oral Bioavailability ◽  
Pharmacokinetic Profile ◽  
Abdominal Sepsis ◽  
Blood Levels ◽  
Population Pharmacokinetic ◽  
Published Data ◽  
Chronic Pulmonary Diseases

Background and Objectives: N-acetylcysteine (NAC) is a mucolytic agent used to prevent ventilator-associated pneumonia in intensive care units. This study aimed to evaluate the oral bioavailability of NAC in critically ill patients with pneumonia, isolated acute brain injury and abdominal sepsis. Materials and Methods: This quantitative and descriptive study compared NAC’s pharmacokinetics after intravenous and enteral administration. 600 mg of NAC was administered in both ways, and the blood levels for NAC were measured. Results: 18 patients with pneumonia, 19 patients with brain injury and 17 patients with abdominal sepsis were included in the population pharmacokinetic modelling. A three-compartmental model without lag-time provided the best fit to the data. Oral bioavailability was estimated as 11.6% (95% confidence interval 6.3–16.9%), similar to bioavailability in healthy volunteers and patients with chronic pulmonary diseases. Conclusions: The bioavailability of enteral NAC of ICU patients with different diseases is similar to the published data on healthy volunteers.

scholarly journals Comparison of oral bioavailability of acetaminophen tablets, capsules and effervescent dosage forms in healthy volunteers

2018 ◽  
Vol 31 (1) ◽  
pp. 5-9 ◽  
Author(s):  
Mona Fathi ◽  
Sohrab Kazemi ◽  
Farbod Zahedi ◽  
Mohamad Reza Shiran ◽  
Ali Akbar Moghadamnia
Keyword(s):  
Healthy Volunteers ◽  
Oral Bioavailability ◽  
Statistical Tests ◽  
Active Material ◽  
Drug Efficacy ◽  
Dosage Forms ◽  
Hplc Method ◽  
Blood Levels ◽  
Moderate Pain ◽  
Blood Samples

AbstractA wide variety of acetaminophen dosage forms have been administered to relieve mild to moderate pain and fever, so far. The purpose of this study was to compare the oral bioavailability in healthy volunteers, of three of these dosage forms. We included healthy volunteers in our study and divided replace with placed them into three groups: tablet, capsule and effervescent. Each dosage form contained 500 mg of acetaminophen as active material. Blood samples were taken at 0.5, 1, 2, 4 and 8-hour intervals after receiving the dose. Acetaminophen blood levels were measured using HPLC method. Data were fit in a “one-compartment PK model”, using P-Pharm 1.5 software and analyzed under statistical tests. The maximum concentrations of acetaminophen in blood samples were measured at 1h after taking the drug (6.61±3.19 μg/ml, 11.29±3.94 μg/ml and 15.25±2.54 μg/ml in groups receiving capsule, tablet and effervescent, respectively). Pharmacokinetic (PK) data analysis & modeling from the three groups showed that the half-life of acetaminophen was 140.72 min in the tablet group, 140.29 min in capsule and 132.08 min in effervescent. The area under the blood levels curve were 47.04, 40.62 and 53.11 μgmin/ml, in tablet, capsule, and effervescent groups, respectively. Statistically significant differences in PK parameters were recorded as the study replace with we compared effervescent with tablets and capsule dosage forms (p < 0.05). According to the results, the effervescent form creates better PK parameters compared with tablet and capsule forms, therefore, it is suggested replace with we suggested that this form should be administer in cases of pain and fever to achieve quick drug efficacy.

One-year costs of intensive care in pediatric patients with traumatic brain injury

2021 ◽  
Vol 27 (1) ◽  
pp. 79-86
Author(s):  
Era D. Mikkonen ◽  
Markus B. Skrifvars ◽  
Matti Reinikainen ◽  
Stepani Bendel ◽  
Ruut Laitio ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Intensive Care ◽  
Brain Injury ◽  
Social Security ◽  
Functional Outcome ◽  
Injury Severity ◽  
Pediatric Population ◽  
Favorable Outcome ◽  
Index Hospitalization ◽  
Pediatric Tbi

OBJECTIVETraumatic brain injury (TBI) is a major cause of death and disability in the pediatric population. The authors assessed 1-year costs of intensive care in pediatric TBI patients.METHODSIn this retrospective multicenter cohort study of four academic ICUs in Finland, the authors used the Finnish Intensive Care Consortium database to identify children aged 0–17 years treated for TBI in ICUs between 2003 and 2013. The authors reviewed all patient health records and head CT scans for admission, treatment, and follow-up data. Patient outcomes included functional outcome (favorable outcome defined as a Glasgow Outcome Scale score of 4–5) and death within 6 months. Costs included those for the index hospitalization, rehabilitation, and social security up to 1 year after injury. To assess costs, the authors calculated the effective cost per favorable outcome (ECPFO).RESULTSIn total, 293 patients were included, of whom 61% had moderate to severe TBI (Glasgow Coma Scale [GCS] score 3–12) and 40% were ≥ 13 years of age. Of all patients, 82% had a favorable outcome and 9% died within 6 months of injury. The mean cost per patient was €48,719 ($54,557) (95% CI €41,326–€56,112). The index hospitalization accounted for 66%, rehabilitation costs for 27%, and social security costs for 7% of total healthcare costs. The ECPFO was €59,727 ($66,884) (95% CI €52,335–€67,120). A higher ECPFO was observed among patients with clinical and treatment-related variables indicative of parenchymal swelling and high intracranial pressure. Lower ECPFO was observed among patients with higher admission GCS scores and those who had epidural hematomas.CONCLUSIONSGreater injury severity increases ECPFO and is associated with higher postdischarge costs in pediatric TBI patients. In this pediatric cohort, over two-thirds of all resources were spent on patients with favorable functional outcome, indicating appropriate resource allocation.

Early mobilization in intensive care for patients with brain injury: e-Survey of current practices in France

2021 ◽  
Author(s):  
François Feuvrier ◽  
Claire Jourdan ◽  
Olivier Barber ◽  
Margrit Ascher ◽  
Karolina Griffiths ◽  
...  
Keyword(s):  
Intensive Care ◽  
Brain Injury ◽  
Early Mobilization ◽  
Current Practices

Emotional Aspects of Pediatric Post-Intensive Care Syndrome Following Traumatic Brain Injury

2021 ◽  
Author(s):  
Kathryn R. Bradbury ◽  
Cydni Williams ◽  
Skyler Leonard ◽  
Emily Holding ◽  
Elise Turner ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Intensive Care ◽  
Brain Injury ◽  
Emotional Aspects ◽  
Post Intensive Care Syndrome

scholarly journals Development of a Prognostic Model to Predict Mortality after Traumatic Brain Injury in Intensive Care Setting in a Developing Country

2021 ◽  
Vol 12 (02) ◽  
pp. 368-375
Author(s):  
Mini Jayan ◽  
Dhaval Shukla ◽  
Bhagavatula Indira Devi ◽  
Dhananjaya I. Bhat ◽  
Subhas K. Konar
Keyword(s):  
Traumatic Brain Injury ◽  
Intensive Care ◽  
Brain Injury ◽  
Hospital Mortality ◽  
Prognostic Model ◽  
Third Ventricle ◽  
The Third ◽  
Scan Data ◽  
Gcs Score ◽  
Basal Cisterns

Abstract Objectives We aimed to develop a prognostic model for the prediction of in-hospital mortality in patients with traumatic brain injury (TBI) admitted to the neurosurgery intensive care unit (ICU) of our institute. Materials and Methods The clinical and computed tomography scan data of consecutive patients admitted after a diagnosis TBI in ICU were reviewed. Construction of the model was done by using all the variables of Corticosteroid Randomization after Significant Head Injury and International Mission on Prognosis and Analysis of Clinical Trials in TBI models. The endpoint was in-hospital mortality. Results A total of 243 patients with TBI were admitted to ICU during the study period. The in-hospital mortality was 15.3%. On multivariate analysis, the Glasgow coma scale (GCS) at admission, hypoxia, hypotension, and obliteration of the third ventricle/basal cisterns were significantly associated with mortality. Patients with hypoxia had eight times, with hypotensions 22 times, and with obliteration of the third ventricle/basal cisterns three times more chance of death. The TBI score was developed as a sum of individual points assigned as follows: GCS score 3 to 4 (+2 points), 5 to 12 (+1), hypoxia (+1), hypotension (+1), and obliteration third ventricle/basal cistern (+1). The mortality was 0% for a score of “0” and 85% for a score of “4.” Conclusion The outcome of patients treated in ICU was based on common admission variables. A simple clinical grading score allows risk stratification of patients with TBI admitted in ICU.

scholarly journals The Association Between Arterial Oxygen Level and Outcome in Neurocritically Ill Patients is not Affected by Blood Pressure

2021 ◽  
Author(s):  
Jaana Humaloja ◽  
Markus B. Skrifvars ◽  
Rahul Raj ◽  
Erika Wilkman ◽  
Pirkka T. Pekkarinen ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Intensive Care ◽  
Brain Injury ◽  
Hemodynamic Instability ◽  
Arterial Oxygen ◽  
Admission Diagnosis ◽  
Secondary Brain Injury ◽  
Multivariable Logistic Regression Model ◽  
Mechanically Ventilated ◽  
The Relationship

Abstract Background In neurocritically ill patients, one early mechanism behind secondary brain injury is low systemic blood pressure resulting in inadequate cerebral perfusion and consequent hypoxia. Intuitively, higher partial pressures of arterial oxygen (PaO2) could be protective in case of inadequate cerebral circulation related to hemodynamic instability. Study purpose We examined whether the association between PaO2 and mortality is different in patients with low compared to normal and high mean arterial pressure (MAP) in patients after various types of brain injury. Methods We screened the Finnish Intensive Care Consortium database for mechanically ventilated adult (≥ 18) brain injury patients treated in several tertiary intensive care units (ICUs) between 2003 and 2013. Admission diagnoses included traumatic brain injury, cardiac arrest, subarachnoid and intracranial hemorrhage, and acute ischemic stroke. The primary exposures of interest were PaO2 (recorded in connection with the lowest measured PaO2/fraction of inspired oxygen ratio) and the lowest MAP, recorded during the first 24 h in the ICU. PaO2 was grouped as follows: hypoxemia (< 8.2 kPa, the lowest 10th percentile), normoxemia (8.2–18.3 kPa), and hyperoxemia (> 18.3 kPa, the highest 10th percentile), and MAP was divided into equally sized tertiles (< 60, 60–68, and > 68 mmHg). The primary outcome was 1-year mortality. We tested the association between hyperoxemia, MAP, and mortality with a multivariable logistic regression model, including the PaO2, MAP, and interaction of PaO2*MAP, adjusting for age, admission diagnosis, premorbid physical performance, vasoactive use, intracranial pressure monitoring use, and disease severity. The relationship between predicted 1-year mortality and PaO2 was visualized with locally weighted scatterplot smoothing curves (Loess) for different MAP levels. Results From a total of 8290 patients, 3912 (47%) were dead at 1 year. PaO2 was not an independent predictor of mortality: the odds ratio (OR) for hyperoxemia was 1.16 (95% CI 0.85–1.59) and for hypoxemia 1.24 (95% CI 0.96–1.61) compared to normoxemia. Higher MAP predicted lower mortality: OR for MAP 60–68 mmHg was 0.73 (95% CI 0.64–0.84) and for MAP > 68 mmHg 0.80 (95% CI 0.69–0.92) compared to MAP < 60 mmHg. The interaction term PaO2*MAP was nonsignificant. In Loess visualization, the relationship between PaO2 and predicted mortality appeared similar in all MAP tertiles. Conclusions During the first 24 h of ICU treatment in mechanically ventilated brain injured patients, the association between PaO2 and mortality was not different in patients with low compared to normal MAP.

scholarly journals Fulvestrant-3-Boronic Acid (ZB716) Demonstrates Oral Bioavailability and Favorable Pharmacokinetic Profile in Preclinical ADME Studies

2021 ◽  
Vol 14 (8) ◽  
pp. 719
Author(s):  
Jiawang Liu ◽  
Nirmal Rajasekaran ◽  
Ahamed Hossain ◽  
Changde Zhang ◽  
Shanchun Guo ◽  
...  
Keyword(s):  
Boronic Acid ◽  
Oral Bioavailability ◽  
Drug Exposure ◽  
Liver Microsomes ◽  
Pharmacokinetic Profile ◽  
Pharmacokinetic Studies ◽  
Dependent Manner ◽  
Mucosal Permeability ◽  
Time Curve ◽  
Concentration Dependent Manner

Fulvestrant-3-boronic acid (ZB716), an oral selective estrogen receptor degrader (SERD) under clinical development, has been investigated in ADME studies to characterize its absorption, metabolism, and pharmacokinetics. ZB716 was found to have high plasma protein binding in human and animal plasma, and low intestinal mucosal permeability. ZB716 had high clearance in hepatocytes of all species tested. ZB716 was metabolized primarily by CYP2D6 and CYP3A. In human liver microsomes, ZB716 demonstrated relatively low inhibition of CYP1A2, 2C8, 2C9, 2C19, 2D6, and 3A4 (when testosterone was used as the substrate), and no inhibition of CYP2B6 and 3A4 (when midazolam was used as the substrate). In assays for enzyme activity, ZB716 induced CYP1A2, 2B6, and 3A4 in a concentration-dependent manner. Single-dose and repeated-dose pharmacokinetic studies in rats and dogs showed oral bioavailability, dose-proportional drug exposure, and drug accumulation as measured by maximum concentration and area under the concentration–time curve (AUC).

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.

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