Clinical Pharmacokinetics of Oral Cephalosporins

2015 ◽  
pp. 34-71 ◽  
Author(s):  
Klaus Stoeckel ◽  
William L. Hayton ◽  
David J. Edwards
Keyword(s):  
Clinical Pharmacokinetics

scholarly journals Clinical Pharmacokinetics of Oral Semaglutide: Analyses of Data from Clinical Pharmacology Trials

2021 ◽  
Author(s):  
Rune V. Overgaard ◽  
Andrea Navarria ◽  
Steen H. Ingwersen ◽  
Tine A. Bækdal ◽  
Rasmus Juul Kildemoes
Keyword(s):  
Clinical Pharmacology ◽  
Clinical Pharmacokinetics

scholarly journals Clinical Pharmacokinetics of Triazoles in Pediatric Patients

2021 ◽  
Author(s):  
Didi Bury ◽  
Wim J. E. Tissing ◽  
Eline W. Muilwijk ◽  
Tom F. W. Wolfs ◽  
Roger J. Brüggemann
Keyword(s):  
Pediatric Patients ◽  
Clinical Pharmacokinetics

scholarly journals Safety and nonclinical and clinical pharmacokinetics of PC945, a novel inhaled triazole antifungal agent

2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Lindsey Cass ◽  
Alison Murray ◽  
Amanda Davis ◽  
Kathy Woodward ◽  
Muna Albayaty ◽  
...  
Keyword(s):  
Antifungal Agent ◽  
Clinical Pharmacokinetics

scholarly journals Clinical Pharmacokinetics and Pharmacodynamics of Selumetinib

2020 ◽  
Author(s):  
Olivia Campagne ◽  
Kee Kiat Yeo ◽  
Jason Fangusaro ◽  
Clinton F. Stewart
Keyword(s):  
Pharmacokinetics And Pharmacodynamics ◽  
Clinical Pharmacokinetics

scholarly journals Which Analysis Approach Is Adequate to Leverage Clinical Microdialysis Data? A Quantitative Comparison to Investigate Exposure and Reponse Exemplified by Levofloxacin

2021 ◽  
Author(s):  
David Busse ◽  
André Schaeftlein ◽  
Alexander Solms ◽  
Luis Ilia ◽  
Robin Michelet ◽  
...  
Keyword(s):  
Drug Exposure ◽  
Visual Predictive Check ◽  
Model Performance ◽  
Compartmental Analysis ◽  
Community Acquired Pneumonia ◽  
Target Site ◽  
Clinical Pharmacokinetics ◽  
Time Integral ◽  
Dosing Regimens ◽  
Therapeutic Decision Making

Abstract Purpose Systematic comparison of analysis methods of clinical microdialysis data for impact on target-site drug exposure and response. Methods 39 individuals received a 500 mg levofloxacin short-term infusion followed by 24-h dense sampling in plasma and microdialysate collection in interstitial space fluid (ISF). ISF concentrations were leveraged using non-compartmental (NCA) and compartmental analysis (CA) via (ii) relative recovery correction at midpoint of the collection interval (midpoint-NCA, midpoint-CA) and (ii) dialysate-based integrals of time (integral-CA). Exposure and adequacy of community-acquired pneumonia (CAP) therapy via pharmacokinetic/pharmacodynamic target-attainment (PTA) analysis were compared between approaches. Results Individual AUCISF estimates strongly varied for midpoint-NCA and midpoint-CA (≥52.3%CV) versus integral-CA (≤32.9%CV) owing to separation of variability in PK parameters (midpoint-CA = 46.5%–143%CVPK, integral-CA = 26.4%–72.6%CVPK) from recovery-related variability only in integral-CA (41.0%–50.3%CVrecovery). This also led to increased variability of AUCplasma for midpoint-CA (56.0%CV) versus midpoint-NCA and integral-CA (≤33.0%CV), and inaccuracy of predictive model performance of midpoint-CA in plasma (visual predictive check). PTA analysis translated into 33% of evaluated patient cases being at risk of incorrectly rejecting recommended dosing regimens at CAP-related epidemiological cut-off values. Conclusions Integral-CA proved most appropriate to characterise clinical pharmacokinetics- and microdialysis-related variability. Employing this knowledge will improve the understanding of drug target-site PK for therapeutic decision-making.

scholarly journals SAT-LB303 Severe Refractory Volume Overload With Diazoxide in the Treatment of Insulinoma

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Pouneh Pasha ◽  
Graydon S Meneilly ◽  
Jordanna Esther Kapeluto
Keyword(s):  
Surgical Resection ◽  
Myocardial Infarct ◽  
Kidney Injury ◽  
Volume Overload ◽  
Cardiorenal Syndrome ◽  
Intermittent Hemodialysis ◽  
Close Monitoring ◽  
Clinical Pharmacokinetics ◽  
Reduced Ejection Fraction ◽  
Supportive Management

Abstract Background: Insulinoma is the most common neuroendocrine tumor (NET), occurring in 1-4 people per million. Surgical resection remains standard of care for symptomatic control and long-term remission. Where surgery is not feasible medical therapy with diazoxide and somatostatin analogues is used as supportive management. Case: A 88-year-old male with background hypertension, remote myocardial infarct and chronic kidney disease (CKD) (Cr 130-150 umol/L; N 60-115) was diagnosed with insulinoma following a presentation for confusion and CBG of 0.9 mmol/L. Diagnosis was confirmed by 72 hour fast with inappropriate insulin (85 pmol/L; N&lt95) and elevated c-peptide (1875 pmol/L; N 325-1090) with documented hypoglycemia (2.8 mmol/L). CT abdomen localized a 1.2 cm exophytic lesion in the pancreatic tail suggestive of insulinoma. Normal morning cortisol (547 nmol/L) excluded adrenal insufficiency. Initial management included resuscitation with dextrose infusions. Due to advanced age and high cardiac risk profile, the patient was not a candidate for surgical resection of the NET. Endoscopic ultrasound (EUS) ablation was deferred at time of initial hospitalization due to stabilization of hypoglycemia with high glycemic diet. An episode of nocturnal hypoglycemia prompted initiation of diazoxide 100 mg as an outpatient. Subsequent dyspnea (NYHA IV) developed and acute on chronic kidney injury (peak Cr 416 umol/L) with evidence of anasarca secondary to diazoxide use prompted readmission to hospital. With conversion to octreotide, discontinuation of diazoxide and treatment with multiple diuretics, volume overload did not improve. The patient was deemed not a candidate for intermittent hemodialysis and the decision was made to change goals of care. The patient died of complications of volume overload from cardiorenal syndrome 21 days after the initiation of diazoxide. Conclusion: Volume overload has been documented as a complication of diazoxide use in both hypoglycemia and hypertension, occurring in up to 50% of cases, however mortality is not common with supportive management.1, 2 Risk factors for refractory volume overload appear to include reduced ejection fraction, extremes of age and history of CKD3. Possible mechanisms for acute decompensation in CKD include increased unbound diazoxide levels, prerenal effect from hypotension and sodium retention4,5. This case highlights the need for close monitoring with diazoxide use in high risk patients. Clinicians should consider echocardiogram, close monitoring of clinical volume status and renal parameters. References: 1) Goode PN. (1986). World J Surg 10: 586. 2) Komatsu Y. (2016) Endocr J. 63(3): 311. 3) Tarçin O. (2018). Endocrine Abstracts56 EP4. 4) Pearson RM. (1977) Clinical Pharmacokinetics vol 2: 198. 5) Allen WR. (1983). Pharmacology 27: 336.

Clinical Pharmacokinetics of Systemic Antifungal Drugs

1983 ◽  
Vol 8 (1) ◽  
pp. 17-42 ◽  
Author(s):  
T. K. Daneshmend ◽  
D. W. Warnock
Keyword(s):  
Antifungal Drugs ◽  
Clinical Pharmacokinetics
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