Predicted Steady State Volume of Distribution Normalized by Body Mass Index

2020 ◽  
Author(s):  
Keyword(s):  
Body Mass Index ◽  
Steady State ◽  
Body Mass ◽  
Volume Of Distribution

Relationships of body mass index with serum carotenoids, tocopherols and retinol at steady-state and in response to a carotenoid-rich vegetable diet intervention in Filipino schoolchildren1

2008 ◽  
Vol 28 (2) ◽  
pp. 97-106 ◽  
Author(s):  
Judy D. Ribaya-Mercado ◽  
Cherry C. Maramag ◽  
Lorena W. Tengco ◽  
Jeffrey B. Blumberg ◽  
Florentino S. Solon
Keyword(s):  
Body Mass Index ◽  
Steady State ◽  
Body Mass ◽  
Dietary Intervention ◽  
Serum Concentrations ◽  
Serum Retinol ◽  
Vegetable Diet ◽  
Diet Intervention ◽  
Β Carotene ◽  
Low Serum

In marginally nourished children, information is scarce regarding the circulating concentrations of carotenoids and tocopherols, and physiological factors influencing their circulating levels. We determined the serum concentrations of carotenoids, tocopherols and retinol at steady state and in response to a 9-week vegetable diet intervention in 9–12-year-old girls (n=54) and boys (n=65) in rural Philippines. We determined cross-sectional relationships of BMI (body mass index) with serum micronutrient levels, and whether BMI is a determinant of serum carotenoid responses to the ingestion of carotenoid-rich vegetables. We measured dietary nutrient intakes and assessed inflammation by measurement of serum C-reactive protein levels. The children had low serum concentrations of carotenoids, tocopherols and retinol as compared with published values for similar-aged children in the U.S.A. The low serum retinol levels can be ascribed to inadequate diets and were not the result of confounding due to inflammation. Significant inverse correlations of BMI and serum all-trans-β-carotene, 13-cis-β-carotene, α-carotene, lutein, zeaxanthin and α-tocopherol (but not β-cryptoxanthin, lycopene and retinol) were observed among girls at baseline. The dietary intervention markedly enhanced the serum concentrations of all carotenoids. Changes in serum all-trans-β-carotene and α-carotene (but not changes in lutein, zeaxanthin and β-cryptoxanthin) in response to the dietary intervention were inversely associated with BMI in girls and boys. Thus, in Filipino school-aged children, BMI is inversely related to the steady-state serum concentrations of certain carotenoids and vitamin E, but not vitamin A, and is a determinant of serum β- and α-carotene responses, but not xanthophyll responses, to the ingestion of carotenoid-rich vegetable meals.

scholarly journals Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency: Alterations in Cortisol Pharmacokinetics at Puberty

2001 ◽  
Vol 86 (6) ◽  
pp. 2701-2708 ◽  
Author(s):  
Evangelia Charmandari ◽  
Peter C. Hindmarsh ◽  
Atholl Johnston ◽  
Charles G. D. Brook
Keyword(s):  
Body Mass Index ◽  
Congenital Adrenal Hyperplasia ◽  
Body Mass ◽  
Half Life ◽  
Volume Of Distribution ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Total Cortisol ◽  
Free Cortisol ◽  
21 Hydroxylase Deficiency

In congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, treatment with glucocorticoid and mineralocorticoid substitution is not always satisfactory. Suboptimal control is often observed in pubertal patients, despite adequate replacement doses and adherence to treatment. We investigated whether the pubertal process is associated with alterations in cortisol pharmacokinetics resulting in a loss of control of the hypothalamic-pituitary-adrenal axis. We determined the pharmacokinetics of hydrocortisone administered iv as a bolus. A dose of 15 mg/m2 body surface area was given to 14 prepubertal (median age, 9.4 yr; range, 6.1–10.8 yr), 20 pubertal (median, 13.5 yr; range, 10.6–16.8 yr), and 6 postpubertal (median, 18.2 yr; range, 17.2–20.3 yr) patients with salt-wasting CAH. All patients were on standard replacement therapy with hydrocortisone and 9α-fludrocortisone. Serum total cortisol concentrations were measured at 10-min intervals for 6 h following iv hydrocortisone bolus and analyzed using a solid-phase RIA. The serum total cortisol clearance curve was monoexponential. Mean clearance was significantly higher in the pubertal group (mean, 427.0 mL/min; sd, 133.4) compared with the prepubertal (mean, 248.7 mL/min; sd, 100.6) and postpubertal (mean, 292.4 mL/min; sd, 106.3) (one-way ANOVA, F = 9.8, P < 0.001) groups. This effect persisted after adjustment for body mass index. The mean volume of distribution was also significantly higher in the pubertal (mean, 49.5 L; sd, 12.2) than the prepubertal (mean, 27.1 L; sd, 8.4) patients but not in the postpubertal (mean, 40.8 L; sd, 16) (ANOVA, F = 15.2, P < 0.001) patients. The significance remained after correction for body mass index. There was no significant difference in mean half-life of total cortisol in prepubertal (mean, 80.2 min; sd, 19.4), pubertal (mean, 84.4 min; sd, 24.9), and postpubertal (mean, 96.7 min; sd, 9.9) patients. Similar differences between groups were observed when the pharmacokinetic parameters of free cortisol were examined. In addition, the half-life of free cortisol was significantly shorter in females compared with males (P = 0.04). These data suggest that puberty is associated with alterations in cortisol pharmacokinetics resulting in increased clearance and volume of distribution with no change in half-life. These alterations probably reflect changes in the endocrine milieu at puberty and may have implications for therapy of CAH and other conditions requiring cortisol substitution in the adolescent years.

scholarly journals Differential Benefit of Adjuvant Docetaxel-Based Chemotherapy in Patients With Early Breast Cancer According to Baseline Body Mass Index

2020 ◽  
Vol 38 (25) ◽  
pp. 2883-2891 ◽  
Author(s):  
Christine Desmedt ◽  
Marco Fornili ◽  
Florian Clatot ◽  
Romano Demicheli ◽  
Davide De Bortoli ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Body Mass Index ◽  
Body Mass ◽  
Disease Free Survival ◽  
Dose Intensity ◽  
Clinical Trial Data ◽  
Volume Of Distribution ◽  
Baseline Body Mass Index ◽  
Docetaxel Group ◽  
Er Status

PURPOSE Lipophilic drugs, such as taxanes, have a high affinity for adipose tissue and a resulting higher volume of distribution. Here, we reanalyzed clinical trial data to investigate whether the efficacy of docetaxel-based chemotherapy differs from non-docetaxel–based chemotherapy in patients with breast cancer according to their baseline body mass index (BMI). PATIENTS AND METHODS We retrospectively analyzed data from all of the patients in the adjuvant BIG 2-98 trial (ClinicalTrials.gov identifier: NCT00174655 ; N = 2,887) comparing non-docetaxel– to docetaxel-containing chemotherapy. BMI (kg/m2) was categorized as follows: 18.5 to < 25, lean; 25 to < 30, overweight; and ≥ 30, obese. Disease-free survival (DFS) was the primary endpoint, and overall survival (OS) was the secondary endpoint. A second-order interaction was assessed among treatment, BMI, and estrogen receptor (ER) status. RESULTS There was no difference in DFS or OS according to BMI in the non-docetaxel group, while reduced DFS and OS were observed with increasing BMI category in the docetaxel group. Adjusted hazard ratios for DFS and OS were, respectively, 1.12 (95% CI, 0.98 to 1.50; P = .21) and 1.27 (95% CI, 1.01 to 1.60; P = .04) for overweight versus lean groups and were 1.32 (95% CI, 1.08 to 1.62; P = .007) and 1.63 (95% CI, 1.27 to 2.09; P < .001), respectively, for obese versus lean groups. Similar results were obtained when considering ER-negative and ER-positive tumors separately and when considering only patients who received a relative dose intensity ≥ 85% for docetaxel. A joint modifying role of BMI and ER status on treatment effect was evident for DFS (adjusted P = .06) and OS (adjusted P = .04). CONCLUSION This retrospective analysis of a large adjuvant trial highlights a differential response to docetaxel according to BMI, which calls for a body composition–based re-evaluation of the risk-benefit ratio of the use of taxanes in breast cancer. These results now must be confirmed in additional series.

scholarly journals Weight Reduction Increases Plasma Levels of an Adipose-Derived Anti-Inflammatory Protein, Adiponectin

2001 ◽  
Vol 86 (8) ◽  
pp. 3815-3819 ◽  
Author(s):  
Wei-Shiung Yang ◽  
Wei-Jei Lee ◽  
Tohru Funahashi ◽  
Sachiyo Tanaka ◽  
Yuji Matsuzawa ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Body Weight ◽  
Steady State ◽  
Body Mass ◽  
Plasma Glucose ◽  
Weight Reduction ◽  
Plasma Levels ◽  
Plasma Adiponectin ◽  
Body Weight Reduction ◽  
Glucose Levels

Adiponectin, an adipose tissue-specific plasma protein, was recently revealed to have anti-inflammatory effects on the cellular components of vascular wall. Its plasma levels were significantly lower in men than in women and lower in human subjects with obesity, type 2 diabetes mellitus, or coronary artery disease. Therefore, it may provide a biological link between obesity and obesity-related disorders such as atherosclerosis, against which it may confer protection. In this study, we observed the changes of plasma adiponectin levels with body weight reduction among 22 obese patients who received gastric partition surgery. A 46% increase of mean plasma adiponectin level was accompanied by a 21% reduction in mean body mass index. The change in plasma adiponectin levels was significantly correlated with the changes in body mass index (r = −0.5, P = 0.01), waist (r = −0.4, P = 0.04) and hip (r =− 0.6, P = 0.0007) circumferences, and steady state plasma glucose levels (r = −0.5, P = 0.04). In multivariate linear regression models, the increase in adiponectin as a dependent variable was significantly related to the decrease in hip circumference (β = −0.16, P = 0.028), after adjusting body mass index and waist circumference. The change in steady state plasma glucose levels as a dependent variable was related to the increase of adiponectin with a marginal significance (β =− 0.92, P = 0.053), after adjusting body mass index and waist and hip circumferences. In conclusion, body weight reduction increased the plasma levels of a protective adipocytokine, adiponectin. In addition, the increase in plasma adiponectin despite the reduction of the only tissue of its own synthesis suggests that the expression of adiponectin is under feedback inhibition in obesity.

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