The Impact of Obesity and Disease on Busulfan Oral Clearance in Adults

Blood ◽  
1999 ◽  
Vol 93 (12) ◽  
pp. 4436-4440
Author(s):  
John P. Gibbs ◽  
Ted Gooley ◽  
Bruce Corneau ◽  
Georgia Murray ◽  
Patricia Stewart ◽  
...  
Keyword(s):  
Body Weight ◽  
Ideal Body Weight ◽  
Normal Weight ◽  
Myelogenous Leukemia ◽  
Obese Patients ◽  
Oral Clearance ◽  
Plasma Level Monitoring ◽  
Ideal Body ◽  
The Impact ◽  
Level Monitoring

The apparent oral clearance (CL/F, mL/min) of busulfan was measured in 279 adolescent and adult patients. Significant (P< .05) determinants of CL/F by linear regression were: actual body weight (BW; r2 = 0.300), body surface area (BSA; r2 = 0.277), adjusted ideal body weight (AIBW; r2 = 0.265), and ideal body weight (IBW; r2= 0.173); whereas body mass index (BMI), height, age, gender, and disease were less important predictors. CL/F (mL/min) for normal weight patients (BMI, 18 to 27 kg/m2) was 16.2% lower (P< .001) than for obese patients (BMI, 27 to 35 kg/m2). Thus, expressing CL/F relative to BW did not eliminate statistically significant differences between normal and obese patients. However, busulfan CL/F expressed relative to BSA (110 ± 24 v 110 ± 24 mL/min/m2, P = 1.0) or AIBW (3.04 ± 0.65 v 3.19 ± 0.67 mL/min/kg, P = .597) were similar in normal and obese patients. Non-Hodgkin’s lymphoma patients (n = 10) had approximately 32% lower mean busulfan CL/F expressed relative to BW, BSA, or AIBW compared with patients with chronic myelogenous leukemia (n = 73). Routine dosing on the basis of BSA or AIBW in adults and adolescents does not require a specific accommodation for the obese. However, dosing based on BSA may be improved by considering CL/F differences in certain diseases. Adjusting dose for body size or disease does not diminish interpatient variability sufficiently to obviate plasma level monitoring in many indications.

The Impact of Obesity and Disease on Busulfan Oral Clearance in Adults

Blood ◽  
1999 ◽  
Vol 93 (12) ◽  
pp. 4436-4440 ◽  
Author(s):  
John P. Gibbs ◽  
Ted Gooley ◽  
Bruce Corneau ◽  
Georgia Murray ◽  
Patricia Stewart ◽  
...  
Keyword(s):  
Body Weight ◽  
Ideal Body Weight ◽  
Normal Weight ◽  
Myelogenous Leukemia ◽  
Obese Patients ◽  
Oral Clearance ◽  
Plasma Level Monitoring ◽  
Ideal Body ◽  
The Impact ◽  
Level Monitoring

Abstract The apparent oral clearance (CL/F, mL/min) of busulfan was measured in 279 adolescent and adult patients. Significant (P&lt; .05) determinants of CL/F by linear regression were: actual body weight (BW; r2 = 0.300), body surface area (BSA; r2 = 0.277), adjusted ideal body weight (AIBW; r2 = 0.265), and ideal body weight (IBW; r2= 0.173); whereas body mass index (BMI), height, age, gender, and disease were less important predictors. CL/F (mL/min) for normal weight patients (BMI, 18 to 27 kg/m2) was 16.2% lower (P&lt; .001) than for obese patients (BMI, 27 to 35 kg/m2). Thus, expressing CL/F relative to BW did not eliminate statistically significant differences between normal and obese patients. However, busulfan CL/F expressed relative to BSA (110 ± 24 v 110 ± 24 mL/min/m2, P = 1.0) or AIBW (3.04 ± 0.65 v 3.19 ± 0.67 mL/min/kg, P = .597) were similar in normal and obese patients. Non-Hodgkin’s lymphoma patients (n = 10) had approximately 32% lower mean busulfan CL/F expressed relative to BW, BSA, or AIBW compared with patients with chronic myelogenous leukemia (n = 73). Routine dosing on the basis of BSA or AIBW in adults and adolescents does not require a specific accommodation for the obese. However, dosing based on BSA may be improved by considering CL/F differences in certain diseases. Adjusting dose for body size or disease does not diminish interpatient variability sufficiently to obviate plasma level monitoring in many indications.

A universal formula based on cystatin C to perform individual dosing of carboplatin in normal weight, underweight, and obese patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 2527-2527
Author(s):  
E. Chatelut ◽  
A. Schmitt ◽  
A. Lansiaux ◽  
C. Bobin-Dubigeon ◽  
M. Etienne-Grimaldi ◽  
...  
Keyword(s):  
Body Weight ◽  
Lean Body Mass ◽  
Body Mass ◽  
Cystatin C ◽  
Ideal Body Weight ◽  
Normal Weight ◽  
Percentage Error ◽  
Pharmacokinetic Analysis ◽  
Obese Patients ◽  
Ideal Body

2527 Background: It has recently been shown that it is possible to improve the prediction of carboplatin clearance by adding plasma cystatin C level (cysC), an endogenous marker of glomerular filtration rate, to the other patient characteristics routinely used for carboplatin individual dosing, namely serum creatinine (Scr), body weight (BW), age, and sex. This multi-center pharmacokinetic study was performed to evaluate prospectively the benefit of using cysC for carboplatin individual dosing. Methods: The 357 patients included in the study were receiving carboplatin as part of established protocols. A population pharmacokinetic analysis was performed using the NONMEM program. Seven covariates were studied: Scr, cysC, age, sex, BW, ideal body weight, and lean body mass. Results: The best covariate equation was: carboplatin clearance (mL/min) = 105. (Scr/75)-0.433. (cysC/1.00)-0.290 . (BW/65)+0.547 . (age/56)-0.351 . 0.855sex, with Scr in μmol/L, cysC in mg/L, BW in kg, age in years, and sex = 0 for male. Using an alternative weight descriptor (ideal body weight or lean body mass) did not improve the prediction. This final covariate model was validated by bootstrap analysis. The bias (mean percentage error) and imprecision (mean absolute percentage error) were +2% and 15% respectively on the total population, and were of a similar magnitude in each of the three subgroups of patients defined according to their body mass index. Conclusions: For the first time, a unique formula is proposed for carboplatin individual dosing to patients which is shown to be equally valid for underweight, normal weight, and obese patients. No significant financial relationships to disclose.

Successful Treatment of Delayed Methotrexate Clearance Using Glucarpidase Dosed on Ideal Body Weight in Obese Patients

2020 ◽  
Vol 40 (5) ◽  
pp. 479-483
Author(s):  
Caroline Krüger ◽  
Nils Engel ◽  
Jochim Reinert ◽  
Winfried Alsdorf ◽  
Walter Fiedler ◽  
...  
Keyword(s):  
Body Weight ◽  
Successful Treatment ◽  
Ideal Body Weight ◽  
Obese Patients ◽  
Ideal Body

Therapeutic Drug Monitoring (TDM) of IV Busulfan in Patients with Severe Obesity.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1990-1990
Author(s):  
Donald A. Hutcherson ◽  
Jolynn K. Sessions ◽  
Ronald A. Mihelic ◽  
Katherine Sanvidge ◽  
Stephen R. Stricker ◽  
...  
Keyword(s):  
Body Weight ◽  
Severe Obesity ◽  
Package Insert ◽  
Ideal Body Weight ◽  
Obese Patients ◽  
Actual Weight ◽  
Severely Obese ◽  
Ideal Body ◽  
The Mean ◽  
Dosing Strategy

Abstract It has been previously reported that increases in relapse and graft rejection can be associated with a low busulfan area under the curve (AUC) and hepatic toxicities are associated with a high AUC. This has lead to strategies to adjust busulfan dosing to achieve a target AUC. A retrospective analysis was performed in patients with severe obesity, defined as a Body Mass Index (BMI) greater than 40, to evaluate the reliability of IV busulfan dosed using the package insert dosing strategy to reach a targeted AUC. The study included 11 females and 8 males who received IV busulfan as part of their hematopoietic progenitor cell transplant preparative regimen. There were 11 autologous and 8 allogeneic transplants for lymphoma (10) and leukemia (9). The mean and median ages were 38 and 41 years (range 19–51). The mean and median BMIs for this population were 47.8 and 46.2 (range 40.4–62.7). The mean and median weights were 139.5 kg and 142.5 kg (range 107–192.3). TDM was performed with the first dose of busulfan along with subsequent dosage adjustments to achieve a target AUC of 1150–1350 micromol X min/L. Busulfex package insert dosing recommendations are for 16 doses of 0.8 mg/kg (12.8 mg/kg) using an adjusted ideal body weight (AIBW) for obese patients. AIBW = 0.25 × (actual weight − ideal body weight) + ideal body weight. Using the AIBW dosing, the mean starting dose to actual body weight ratio was 0.48 mg/kg (range 0.40–0.55 mg/kg). Based on the AUC analysis, the predicted mean AUC using the AIBW dosing was 972 (range 702–1356). Six AUCs were below 900, 10 AUCs were above 900 but below 1150, 2 AUCs were within the target range and 1 AUC was greater than 1350. Thirteen of the patients had repeat AUC analyses following a subsequent dose to confirm that the dose adjustments achieved the targeted AUCs. Seven of these patients had further dose adjustments following the repeat AUC analysis. Five patients with a busulfan mean half-life of 235 minutes (range 218–247 minutes) had higher AUCs than the rest of the group. The mean and median AUCs for these 5 patients were 1177 and 1223 (range 997–1357). The remaining 14 patients with a mean busulfan half-life of 177 minutes (range 151–201) had mean and median AUCs of 899 and 903 (range 702–1105). The total therapy delivered ranged from 12.7 to 21.4 mg/kg based on the AIBW. When calculated on actual weight, the range was 6.9 to 11.24 mg/kg. Conclusion: The AIBW dosing strategy of IV busulfan is inadequate to achieve the targeted AUC of 1150–1350 in severely obese patients. Severely obese patients require dose increases in the majority of cases, while those with delayed clearance could be overdosed if higher doses are administered without TDM. Severely obese patients require TDM and the majority will require dosage adjustments to administer IV busulfan in the targeted therapeutic range.

Effects of Underfeeding and of Starvation on Thermoregulatory Responses to Cooling in Women

1989 ◽  
Vol 77 (3) ◽  
pp. 245-252 ◽  
Author(s):  
P. I. Mansell ◽  
I. A. Macdonald
Keyword(s):  
Body Weight ◽  
Central Body ◽  
Ideal Body Weight ◽  
Young Female ◽  
Normal Weight ◽  
Fed State ◽  
Young Females ◽  
Thermoregulatory Responses ◽  
Ideal Body ◽  
Thermogenic Response

1. The effects of acute alterations in energy intake on the thermoregulatory responses to a cooling stimulus were studied in healthy, normal weight, young female subjects. On separate occasions, seven subjects were underfed for 7 days at 60 kJ day−1 kg−1 ideal body weight and six subjects were starved for 48 h. The cooling stimulus was provided by a coverall perfused with water at 16°C. 2. After the application of the cooling stimulus, central body (auditory canal) temperature rose initially in both studies. After underfeeding, the magnitude of this rise in temperature was not significantly different from that seen in the normally fed state. After 48 h starvation, the rise in temperature on cooling was reduced from 0.30 (sem 0.03) to 0.10 (0.04)°C (P < 0.01). In two subjects in whom central body temperature had been maintained in the normally fed state, a fall occurred after starvation. 3. Underfeeding for 7 days did not affect thermogenesis or the degree of vasoconstriction in the forearm or hand in response to cooling. 4. After 48 h starvation, the thermogenic response to cooling was abolished and blood flow in the forearm remained higher than in the normally fed state. 5. In normal weight young females, thermoregulatory responses to a cooling stimulus were therefore substantially affected by 48 h starvation but not by 7 days underfeeding.

scholarly journals Clinical-epidemiological evaluation in overweight and obese patients after “DCD method” application

2009 ◽  
Vol 3 (1) ◽  
pp. 33-41
Author(s):  
Marina Conese ◽  
Grace Massiah ◽  
Piero Oberto De Cavi
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Quality Improvement ◽  
Who Classification ◽  
Life Quality ◽  
Ideal Body Weight ◽  
Obese Patients ◽  
Ideal Body ◽  
Epidemiological Evaluation ◽  
Dietary Education

The article describes an experimental observation performed for 2 years on 200 patients: 150 female and 50 male between 25 and 65 years old, overweight with class I, II and III obesity (WHO classification). Patients with overt diabetic pathology and with “borderline” hyperglycemia, hypertriglyceridemia and hypercholesterolemia are subjected to “DCD method” (appropriate dietary education associated to New-Electrosculpture) in Bari (DCD office). The aim of the study is weight loss, with patients’ life quality improvement. What we have obtained is an ideal body weight recover without anti-obesity drug use, with maintenance of the results obtained for 18 months.

scholarly journals Strategy to calculate magnesium sulfate dose in obese patients: A randomized blind trial

2021 ◽  
Author(s):  
Sebastião E. Silva Filho ◽  
Omar S. Klinsky ◽  
Joaquim E. Vieira
Keyword(s):  
Body Weight ◽  
Laparoscopic Cholecystectomy ◽  
Magnesium Sulfate ◽  
Postoperative Period ◽  
Ideal Body Weight ◽  
Morphine Consumption ◽  
Control Group ◽  
Obese Patients ◽  
Pain Scores ◽  
Ideal Body

Abstract BACKGROUNDMagnesium sulfate has analgesic properties in the postoperative period. Among obese patients, there is a gap in the knowledge of its pharmacology related to the use of real, ideal, or corrected ideal body weight in calculating its dose. This trial compared postoperative analgesia using actual and corrected ideal body weight.METHODSSeventy-five obese patients scheduled to undergo laparoscopic cholecystectomy under general anesthesia were randomly assigned to three groups. Patients in the control group received no magnesium sulfate; patients in the other two groups received magnesium sulfate 40 mg·kg− 1 of actual body weight or corrected ideal body weight. A ten nonobese patients group helped us as a model of the expected blood magnesium concentration after magnesium sulfate administration in general population.RESULTSPatients from the groups receiving magnesium sulfate showed significant reduction in morphine consumption (p ≤ 0.001) and pain scores (p = 0.006) in the postoperative period compared to the control group. There was no significant difference in the consumption of morphine (p = 0.323) or pain scores (p = 0.082) between these groups. There was no difference in the total duration of neuromuscular block induced by cisatracurium among the three groups (p = 0.181) or in the blood magnesium concentrations throughout the study.CONCLUSIONSMagnesium sulfate decreased postoperative pain and morphine consumption without affecting cisatracurium recovery time in obese patients undergoing laparoscopic cholecystectomy. Analgesic profile was similar in groups receiving magnesium sulfate calculated through real or corrected ideal body weight.TRIAL REGISTRATIONclinicaltrials.gov NCT04003688. (Date of registration: June 24, 2019)

Chemotherapy Dose Adjustment For Obese Patients Undergoing Hematopoietic Stem Cell Transplantation (HSCT): A Survey On Behalf Of The ALWP Of The EBMT

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4535-4535
Author(s):  
Noga Shem-Tov ◽  
Myriam Labopin ◽  
Leila Moukhtari ◽  
Fabio Ciceri ◽  
Jordi Esteve ◽  
...  
Keyword(s):  
Body Weight ◽  
Actual Body ◽  
Dose Adjustment ◽  
Ideal Body Weight ◽  
High Dose ◽  
Obese Patients ◽  
Actual Body Weight ◽  
Hematopoietic Stem ◽  
Chemotherapy Dose ◽  
Ideal Body

Rates of obesity have substantially increased in recent years. Pharmacokinetics of drugs including chemotherapy is different in obese patients due to alteration in the clearance and volume of distribution. Thus, appropriate chemotherapy dosing for obese patients with malignant diseases is a significant issue. Limiting chemotherapy doses in overweight and obese patients may negatively influence the outcomes in these patients. ASCO has recently published clinical practice guidelines for conventional chemotherapy dosing for obese patients with cancer indicating that up to 40% of obese patients received reduced chemotherapy doses that are not based on actual body weight (ABW) [Grigg A, JCO 2012]. Concerns about toxicity or overdosing in obese patients, based on the use of ABW, are unfounded. Moreover, there is a paucity of information addressing the pharmacokinetics of high dose chemotherapy in obese patients undergoing hematopoietic stem cell transplantation (HSCT). A rather small international survey of drug dosing schemes among transplant centers revealed that there is no consensus regarding appropriate dose adjustment for obese patients [Grigg A, Leuk Lymphoma 1997]. Also, there is limited data on outcomes in obese versus non-obese patients in various small retrospective studies. For this reason, the ALWP of the EBMT constructed an electronic survey for assessing current practice of dose adjustment of chemotherapy in patients undergoing HSCT, in transplant centers and for planning retrospective analysis and prospective studies in the future. Fifty six EBMT centers from 27 countries filled the online survey. Among the 56 centers, the percentage of obese patients was less than 10% in 22 centers (40%), between 10 to 19% in 23 centers (42%) and more than 20% in 10 centers (17%). Forty five centers declared they adjust chemotherapy dose for obese patients (80.5%) and only 11 (19.5%) declared they do not adjust dose. Among centers which adjust dose, most uses BMI as the parameter for defining obesity (28 centers, 62%), others use percentage over the actual body weight (ABW) as the basis for defining obesity (11 centers, 24.5%), both BMI and ABW (3 centers, 6.7%) or other parameter (3 centers, 6.7%). Most of the centers that use BMI for adjusting dose define BMI > 30 kg/m2 as the cut-off value (formal definition for obesity), only one center uses morbid obesity (BMI > 40 kg/m2), and the remainder uses other cut-off values. Among 11 centers who use ABW, 9 use ABW more than 120% of ideal body weight for adjustment. Eighty four percents of the centers use one level of obesity for adjustment while the rest uses 2 levels. The method for determining the weight for chemotherapy calculation was actual body weight (ABW) in 16 centers, ideal body weight (IBW) in 10 centers, IBW + 25% of difference between IBW and ABW (IBW+0.25*(ABW-IBW)) in 16 centers and other methods in the rest. Among centers that use dose adjustment, 44% also cap the dose at 2 m2 for chemotherapy dose based on BSA while 56% do not cap. On the contrary, most of the centers (9/11) that do not adjust dose for weight also do not cap the BSA at 2 m2. Seventy nine percents of responding centers use the same approach to dose adjustments for myeloablative, reduced intensity (RIC) or non myeloablative (NMA) conditioning, while 21% reduce the dose less for RIC or NMA conditioning. For Busulfan dose only 7 centers monitor pharmacokinetics (pk). Eleven centers use ideal body weight for calculation, 17 centers use actual weight and 18 centers correct weight according to percentage over actual body weight. Conclusion This EBMT survey reveal large diversity among transplant centers regarding dose adjustment practice for high dose conditioning chemotherapy. Most of the EBMT centers use dose adjustment for obese patients and about half of them also cap BSA at 2 m2, while capping is uncommon in the centers that do not adjust dose. Thus, the range of the final dose is very wide. Even for Busulfan where dose is calculated normally according to ideal body weight, the diversity of dose given for obese patients is wide. Our next step is to analyze outcomes of transplantation according to dose adjustment practice and subsequently to formulate a methodology for future prospective studies. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Comparative evaluation of atracurium dosed on ideal body weight vs. total body weight in morbidly obese patients

2010 ◽  
Vol 71 (1) ◽  
pp. 34-40 ◽  
Author(s):  
Simone Van Kralingen ◽  
Ewoudt M. W. Van De Garde ◽  
Catherijne A. J. Knibbe ◽  
Jeroen Diepstraten ◽  
Marinus J. Wiezer ◽  
...  
Keyword(s):  
Body Weight ◽  
Comparative Evaluation ◽  
Ideal Body Weight ◽  
Total Body Weight ◽  
Morbidly Obese ◽  
Obese Patients ◽  
Ideal Body ◽  
Total Body

Comparison of Predicted and Measured Energy Expenditure in Mechanically Ventilated Obese Patients

1995 ◽  
Vol 11 (2) ◽  
pp. 47-49 ◽  
Author(s):  
Helen M. O'Connell ◽  
Brian L. Erstad
Keyword(s):  
Body Weight ◽  
Medical Center ◽  
Ideal Body Weight ◽  
Obese Patients ◽  
Mechanically Ventilated ◽  
Measured Energy ◽  
Ideal Body ◽  
Mean Differences ◽  
Caloric Requirements ◽  
Ventilated Patients

Objective: To test the appropriateness of using actual body weight (ABW), ideal body weight (IBW), or an adjusted weight for predicting caloric requirements in moderately obese, mechanically ventilated patients receiving parenteral or enteral nutrition. Design: Prospective, nonrandomized pilot study involving seven patients. Setting: University medical center. Main Outcome Measures: Predicted caloric requirements based on ABW, IBW, or an adjusted weight were compared with measured requirements by indirect calorimetry after parenteral nutrition or tube feedings were at goal rate for 24–72 hours. Results: Mean differences between predicted and measured energy requirements for ABW, IBW, and adjusted weight were 821 ± 556 (p < 0.05), −256 ± 493, and 182 ± 501 kcal/d, respectively. Conclusions: Until additional studies are available, IBW or adjusted weight should be used for calculating caloric requirements in the moderately obese patient being mechanically ventilated when actual measurements are not available.

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