Perioperative Glucocorticoid Therapy for Patients with Adrenal Insufficiency: Dosing Based on Pharmacokinetic Data

2020 ◽  
Vol 105 (3) ◽  
pp. e753-e761 ◽  
Author(s):  
Baha M Arafah
Keyword(s):  
Adrenal Insufficiency ◽  
Half Life ◽  
Current Practice ◽  
Volume Of Distribution ◽  
Glucocorticoid Therapy ◽  
Major Surgery ◽  
Pharmacokinetic Data ◽  
Healthy Individuals ◽  
Hormone Injection ◽  
Range Of Values

Abstract Background Perioperative glucocorticoid therapy for patients with adrenal insufficiency (AI) is currently based on anecdotal reports, without supporting pharmacokinetic data. Methods We determined the half-life, clearance, and volume of distribution of 2 consecutive intravenously (IV)-administered doses of hydrocortisone (15 or 25 mg every 6 hours) to 22 dexamethasone-suppressed healthy individuals and used the data to develop a novel protocol to treat 68 patients with AI who required surgical procedures. Patients received 20 mg of hydrocortisone orally 2 to 4 hours before intubation and were started on 25 mg of IV hydrocortisone every 6 hours for 24 hours and 15 mg every 6 hours during the second day. Nadir cortisol concentrations were repeatedly measured during that period. Results In healthy individuals, cortisol half-life was longer when the higher hydrocortisone dose was administered (2.02 ± 0.15 vs 1.81 ± 0.11 hours; P < 0.01), and in patients with AI, the half-life was longer than in healthy individuals given the same hydrocortisone dose. In both populations, the cortisol half-life increased further with the second hormone injection. Prolongation of cortisol half-life was due to decreased hydrocortisone clearance and an increase in its volume of distribution. Nadir cortisol levels determined throughout the 48 postoperative hours were within the range of values and often exceeded those observed perioperatively in patients without adrenal dysfunction. Conclusions Cortisol pharmacokinetics are altered in the postoperative period and indicate that lower doses of hydrocortisone can be safely administered to patients with AI undergoing major surgery. The findings of this investigation call into question the current practice of administering excessive glucocorticoid supplementation during stress.

scholarly journals SAT-391 Perioperative Glucocorticoid Therapy for Patients with Adrenal Insufficiency: Dosing Based on Hydrocortisone Pharmacokinetic Data

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Marie-Noel Rahhal ◽  
Rouba Kortbawi ◽  
Yosra Moria ◽  
Nasser Gharaibeh ◽  
Tombra Govina ◽  
...  
Keyword(s):  
Adrenal Insufficiency ◽  
Glucocorticoid Therapy ◽  
Pharmacokinetic Data

scholarly journals Propofol

2008 ◽  
Vol 109 (6) ◽  
pp. 1132-1136 ◽  
Author(s):  
Paul F. White ◽  
David S. Warner
Keyword(s):  
Half Life ◽  
Compartment Model ◽  
Volume Of Distribution ◽  
Major Surgery ◽  
Anesthetic Technique ◽  
General Anesthetic ◽  
Clearance Rates ◽  
Elimination Half Life ◽  
Elimination Half ◽  
Total Body

Pharmacokinetics and pharmacodynamics of propofol infusions during general anesthesia. By Audrey Shafer, Van A. Doze, Steven L. Shafer, and Paul F. White. Anesthesiology 1988; 69:348-56. Reprinted with permission.The pharmacokinetic and pharmacodynamic properties of propofol (Diprivan) were studied in 50 elective surgical patients. Propofol was administered as a bolus dose, 2 mg/kg iv, followed by a variable-rate infusion, 0-20 mg/min, and intermittent supplemental boluses, 10-20 mg iv, as part of a general anesthetic technique that included nitrous oxide, meperidine, and muscle relaxants. For a majority of the patients (n = 30), the pharmacokinetics of propofol were best described by a two-compartment model. The propofol mean total body clearance rate was 2.09 +/- 0.65 l/min (mean +/- SD), the volume of distribution at steady state was 159 +/- 57 l, and the elimination half-life was 116 +/- 34 min. Elderly patients (patients older than 60 yr vs. those younger than 60 yr) had significantly decreased clearance rates (1.58 +/- 0.42 vs. 2.19 +/- 0.64 l/min), whereas women (vs. men) had greater clearance rates (33 +/- 8 vs. 26 +/- 7 ml x kg x min ) and volumes of distribution (2.50 +/- 0.81 vs. 2.05 +/- 0.65 l/kg). Patients undergoing major (intraabdominal) surgery had longer elimination half-life values (136 +/- 40 vs. 108 +/- 29 min). Patients required an average blood propofol concentration of 4.05 +/- 1.01 micrograms/ml for major surgery and 2.97 +/- 1.07 micrograms/ml for nonmajor surgery. Blood propofol concentrations at which 50% of patients (EC50) were awake and oriented after surgery were 1.07 and 0.95 microgram/ml, respectively. Psychomotor performance returned to baseline at blood propofol concentrations of 0.38-0.43 microgram/ml (EC50). This clinical study demonstrates the feasibility of performing pharmacokinetic and pharmacodynamic analyses when complex infusion and bolus regimens are used for administering iv anesthetics.

scholarly journals The pharmacokinetics of [18F]UCB-H revisited in the healthy non-human primate brain

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sébastien Goutal ◽  
Martine Guillermier ◽  
Guillaume Becker ◽  
Mylène Gaudin ◽  
Yann Bramoullé ◽  
...  
Keyword(s):  
Slow Component ◽  
Specific Binding ◽  
Compartment Model ◽  
Brain Regions ◽  
Volume Of Distribution ◽  
Pharmacokinetic Data ◽  
Limited Information ◽  
Positron Emission ◽  
Human Primate

Abstract Background Positron Emission Tomography (PET) imaging of the Synaptic Vesicle glycoprotein (SV) 2A is a new tool to quantify synaptic density. [18F]UCB-H was one of the first promising SV2A-ligands to be labelled and used in vivo in rodent and human, while limited information on its pharmacokinetic properties is available in the non-human primate. Here, we evaluate the reliability of the three most commonly used modelling approaches for [18F]UCB-H in the non-human cynomolgus primate, adding the coupled fit of the non-displaceable distribution volume (VND) as an alternative approach to improve unstable fit. The results are discussed in the light of the current state of SV2A PET ligands. Results [18F]UCB-H pharmacokinetic data was optimally fitted with a two-compartment model (2TCM), although the model did not always converge (large total volume of distribution (VT) or large uncertainty of the estimate). 2TCM with coupled fit K1/k2 across brain regions stabilized the quantification, and confirmed a lower specific signal of [18F]UCB-H compared to the newest SV2A-ligands. However, the measures of VND and the influx parameter (K1) are similar to what has been reported for other SV2A ligands. These data were reinforced by displacement studies using [19F]UCB-H, demonstrating only 50% displacement of the total [18F]UCB-H signal at maximal occupancy of SV2A. As previously demonstrated in clinical studies, the graphical method of Logan provided a more robust estimate of VT with only a small bias compared to 2TCM. Conclusions Modeling issues with a 2TCM due to a slow component have previously been reported for other SV2A ligands with low specific binding, or after blocking of specific binding. As all SV2A ligands share chemical structural similarities, we hypothesize that this slow binding component is common for all SV2A ligands, but only hampers quantification when specific binding is low.

Comparative metabolic clearance rate, volume of distribution and plasma half-life of human β-lipotropin and acth

Life Sciences ◽  
1978 ◽  
Vol 23 (23) ◽  
pp. 2323-2330 ◽  
Author(s):  
Anthony S. Liotta ◽  
Choh Hao Li ◽  
George C. Schussler ◽  
Dorothy T. Krieger
Keyword(s):  
Clearance Rate ◽  
Half Life ◽  
Volume Of Distribution ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Plasma Half Life

3. Half-Life and Volume of Distribution

1968 ◽  
Vol 2 (5) ◽  
pp. 126-133 ◽  
Author(s):  
John G. Wagner
Keyword(s):  
Half Life ◽  
Volume Of Distribution

scholarly journals EXTENSIVE EXPERTISE IN ENDOCRINOLOGY: Adrenal crisis

2015 ◽  
Vol 172 (3) ◽  
pp. R115-R124 ◽  
Author(s):  
Bruno Allolio
Keyword(s):  
Patient Education ◽  
Adrenal Insufficiency ◽  
Well Being ◽  
Stressful Events ◽  
Major Surgery ◽  
Adrenal Crisis ◽  
Self Administration ◽  
Necrosis Factor Alpha ◽  
Hydrocortisone Administration ◽  
Glucocorticoid Deficiency

Adrenal crisis is a life-threatening emergency contributing to the excess mortality of patients with adrenal insufficiency. Studies in patients on chronic replacement therapy for adrenal insufficiency have revealed an incidence of 5–10 adrenal crises/100 patient years and suggested a mortality rate from adrenal crisis of 0.5/100 patient years. Patients with adrenal crisis typically present with profoundly impaired well-being, hypotension, nausea and vomiting, and fever responding well to parenteral hydrocortisone administration. Infections are the major precipitating causes of adrenal crisis. Lack of increased cortisol concentrations during infection enhances pro-inflammatory cytokine release and sensitivity to the toxic effects of these cytokines (e.g. tumour necrosis factor alpha). Furthermore, pro-inflammatory cytokines may impair glucocorticoid receptor function aggravating glucocorticoid deficiency. Treatment of adrenal crisis is simple and highly effective consisting of i.v. hydrocortisone (initial bolus of 100 mg followed by 200 mg over 24 h as continuous infusion) and 0.9% saline (1000 ml within the first hour). Prevention of adrenal crisis requires appropriate hydrocortisone dose adjustments to stressful medical procedures (e.g. major surgery) and other stressful events (e.g. infection). Patient education is a key for such dose adjustments but current education concepts are not sufficiently effective. Thus, improved education strategies are needed. Every patient should carry an emergency card and should be provided with an emergency kit for parenteral hydrocortisone self-administration. A hydrocortisone pen would hold a great potential to lower the current barriers to hydrocortisone self-injection. Improved patient education and measures to facilitate parenteral hydrocortisone self-administration in impending crisis are expected to significantly reduce morbidity and mortality from adrenal crisis.

scholarly journals Pharmacokinetics of Once Daily Intraperitoneal Cefazolin in Continuous Ambulatory Peritoneal Dialysis Patients

2000 ◽  
Vol 11 (6) ◽  
pp. 1117-1121
Author(s):  
CHAI LUAN LOW ◽  
KAMANI GOPALAKRISHNA ◽  
WAI CHOONG LYE
Keyword(s):  
Peritoneal Dialysis ◽  
Continuous Ambulatory Peritoneal Dialysis ◽  
Half Life ◽  
Volume Of Distribution ◽  
Hplc Method ◽  
Dialysis Patients ◽  
Suitable Alternative ◽  
Once Daily ◽  
Cefazolin Sodium ◽  
Plasma Half Life

Abstract. This study determined the pharmacokinetic characteristics of once daily intraperitoneal (IP) cefazolin in continuous ambulatory peritoneal dialysis (CAPD) patients. Each of the 10 volunteer CAPD patients without active peritonitis received a single IP dose of 1 g of cefazolin sodium for a 6-h dwell. All patients underwent a fixed CAPD regimen comprising a first 6-h dwell followed by two 3-h dwells and a final 12-h overnight dwell. Blood and dialysate samples were collected at 0, 0.5, 1, 2, 3, 6 (end of first dwell), and 24 h after the administration of IP cefazolin. Any urine produced was collected over the 24-h study period. A validated HPLC method was used to analyze cefazolin in plasma, dialysate, and urine. The bioavailability was found to be 77.9 ± 3.1%, volume of distribution 0.20 ± 0.05 L/kg, and plasma half-life 39.9 ± 25.4 h. Mean total, renal, and peritoneal clearances were 4.5 ± 2.3, 1.4 ± 1.1, and 3.5 ± 1.8 ml/min, respectively. Mean plasma and dialysate concentrations at 24 h were 42.8 ± 14.3 and 31.8 ± 11.7 mcg/ml, respectively, well above the minimum inhibitory concentrations (MIC) of susceptible organisms. A once daily IP cefazolin dose of 500 mg/L gave desirable pharmacokinetic attributes for use as a suitable alternative to vancomycin for empiric treatment of CAPD-associated peritonitis.

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