scholarly journals Pharmacokinetics of Intravenous Linezolid in Moderately to Morbidly Obese Adults

2012 ◽  
Vol 57 (3) ◽  
pp. 1144-1149 ◽  
Author(s):  
Amira A. Bhalodi ◽  
Pavlos K. Papasavas ◽  
Darren S. Tishler ◽  
David P. Nicolau ◽  
Joseph L. Kuti
Keyword(s):  
Body Weight ◽  
Ideal Body Weight ◽  
Total Body Weight ◽  
Compartment Model ◽  
Central Compartment ◽  
Volume Of Distribution ◽  
Lean Body Weight ◽  
Morbidly Obese ◽  
Total Body ◽  
Nonobese Patients

ABSTRACTThe pharmacokinetics of linezolid was assessed in 20 adult volunteers with body mass indices (BMI) of 30 to 54.9 kg/m2receiving 5 intravenous doses of 600 mg every 12 h. Pharmacokinetic analyses were conducted using compartmental and noncompartmental methods. The mean (±standard deviation) age, height, and weight were 42.2 ± 12.2 years, 64.8 ± 3.5 in, and 109.5 ± 18.2 kg (range, 78.2 to 143.1 kg), respectively. Linezolid pharmacokinetics in this population were best described by a 2-compartment model with nonlinear clearance (original value, 7.6 ± 1.9 liters/h), which could be inhibited to 85.5% ± 12.2% of its original value depending on the concentration in an empirical inhibition compartment, the volume of the central compartment (24.4 ± 9.6 liters), and the intercompartment transfer constants (K12andK21) of 8.04 ± 6.22 and 7.99 ± 5.46 h−1, respectively. The areas under the curve for the 12-h dosing interval (AUCτ) were similar between moderately obese and morbidly obese groups: 130.3 ± 60.1 versus 109.2 ± 25.5 μg · h/ml (P= 0.32), and there was no significant relationship between the AUC or clearance and any body size descriptors. A significant positive relationship was observed for the total volume of distribution with total body weight (r2= 0.524), adjusted body weight (r2= 0.587), lean body weight (r2= 0.495), and ideal body weight (r2= 0.398), but not with BMI (r2= 0.171). Linezolid exposure in these obese participants was similar overall to that of nonobese patients, implying that dosage adjustments based on BMI alone are not required, and standard doses for patients with body weights up to approximately 150 kg should provide AUCτ values similar to those seen in nonobese participants.

P0264ASSESSMENT OF GFR IN MORBIDLY OBESE PATIENTS USING DIFFERENT EQUATIONS: WHICH IS THE BEST?

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Alaa Sabry ◽  
Amir Basiony ◽  
Mohamed Kamal
Keyword(s):  
Body Weight ◽  
Creatinine Clearance ◽  
Glomerular Filtration ◽  
Total Body Weight ◽  
Lean Body Weight ◽  
Morbidly Obese ◽  
Obese Patients ◽  
Morbidly Obese Patient ◽  
Gault Formula ◽  
Total Body

Abstract Background and Aims Obesity is a potent risk factor for the development of kidney disease. The prevalence of abdominal obesity in Egyptians based upon the European cut-off points was 30.2% for men and 70.9% for women. To detect the best formula for estimation of glomerular filtration rates in morbidly obese individuals. Method: In this prospective study 82 morbidly obese patients were included, Age: 15 to 65 years, Morbidly obese patient (BMI > 40 Kg/m2), Creatinine clearance calculated from a 24-h urine was done, Estimated glomerular filtration rate (eGFR): It was assessed to be correlated with creatinine clearance and detect the most suitable formula for morbidly obese patients. Cockcroft-Gault formula:  Cockcroft-Gault formula (for total body weight): ockcroft-Gault formula (for adjusted body weight): Cockcroft-Gault formula (for lean body weight), MDRD-eGFR (Modification of Diet in Renal Disease equation) (Shahbaz & Gupta, 2019), CKD-epidemiology (CKD-EPI): (Levey, et al, 2009) Results Demogrphic criteria of the studdied patients Conclusion: The equations that had the nearest values to creatinine clearance were CG-TBW-GFR and CGAjBW- GFR, both of them had a moderate reliability with more agreement for the CG-TBW-GFR equation . The CG-TBW-GFR formula was the most reliable one to measure GFR, followed by the CG-AjBW-GFR formula, while the CG-IBW, CG-LBW, MDRD-GFR and CKD-EPI-GFR formulae were not reliable at all .

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

scholarly journals Pharmacokinetics of Telavancin in Adult Patients with Cystic Fibrosis during Acute Pulmonary Exacerbation

2019 ◽  
Vol 64 (1) ◽  
Author(s):  
James M. Kidd ◽  
Colleen M. Sakon ◽  
Louise-Marie Oleksiuk ◽  
Jeffrey J. Cies ◽  
Rebecca S. Pettit ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Body Weight ◽  
Total Body Weight ◽  
Central Compartment ◽  
Volume Of Distribution ◽  
Peripheral Compartment ◽  
Population Pharmacokinetic ◽  
Minimal Risk ◽  
Content Type ◽  
Total Body

ABSTRACT Adults with cystic fibrosis (CF) frequently harbor Staphylococcus aureus, which is increasingly antibiotic resistant. Telavancin is a once-daily rapidly bactericidal antibiotic active against methicillin-, linezolid-, and ceftaroline-resistant S. aureus. Because CF patients experience alterations in pharmacokinetics, the optimal dose of telavancin in this population is unknown. Adult CF patients (n = 18) admitted for exacerbations received 3 doses of telavancin 7.5 mg/kg of body weight (first 6 patients) or 10 mg/kg (final 12 patients) every 24 h (q24h). Population pharmacokinetic models with and without covariates were fitted using the nonparametric adaptive grid algorithm in Pmetrics. The final model was used to perform 5,000-patient Monte Carlo simulations for multiple telavancin doses. The best fit was a 2-compartment model describing the volume of distribution of the central compartment (Vc) as a multiple of total body weight (TBW) and the volume of distribution of the central compartment scaled to total body weight (Vθ) normalized by the median observed value (Vc = Vθ × TBW/52.1) and total body clearance (CL) as a linear function of creatinine clearance (CRCL) (CL = CLNR + CLθ × CRCL), where CLNR represents nonrenal clearance and CLθ represents the slope term on CRCL to estimate renal clearance. The mean population parameters were as follows: Vθ, 4.92  ± 0.76 liters · kg−1; CLNR, 0.59  ± 0.30 liters · h−1; CLθ, 5.97 × 10−3 ± 1.24 × 10−3; Vp (volume of the peripheral compartment), 3.77  ± 1.41 liters; Q (intercompartmental clearance), 4.08  ± 2.17 liters · h−1. The free area under the concentration-time curve (fAUC) values for 7.5 and 10 mg/kg were 30  ± 4.6 and 52  ± 12 mg · h/liter, respectively. Doses of 7.5 mg/kg and 10 mg/kg achieved 76.5% and 100% probability of target attainment (PTA) at a fAUC/MIC threshold of >215, respectively, for MIC of ≤0.12 mg/liter. The probabilities of reaching the acute kidney injury (AKI) threshold AUC (763 mg · h · liter−1) for these doses were 0% and 0.96%, respectively. No serious adverse events occurred. Telavancin 10 mg/kg yielded optimal PTA and minimal risk of AKI, suggesting that this FDA-approved dose is appropriate to treat acute pulmonary exacerbations in CF adults. (The clinical trial discussed in this study has been registered at ClinicalTrials.gov under identifier NCT03172793.)

scholarly journals A Large Impact of Obesity on the Disposition of Ivermectin, Moxidectin and Eprinomectin in a Canine Model: Relevance for COVID-19 Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Alain Bousquet-Mélou ◽  
Anne Lespine ◽  
Jean-François Sutra ◽  
Isabelle Bargues ◽  
Pierre-Louis Toutain
Keyword(s):  
Body Weight ◽  
Steady State ◽  
Obese Subject ◽  
Control Period ◽  
Total Body Weight ◽  
Canine Model ◽  
Volume Of Distribution ◽  
Lean Body Weight ◽  
Total Body

Ivermectin (IVM) and moxidectin (MOX) are used extensively as parasiticides in veterinary medicine. Based on in vitro data, IVM has recently been proposed for the prevention and treatment of COVID-19 infection, a condition for which obesity is a major risk factor. In patients, IVM dosage is based on total body weight and there are no recommendations to adjust dosage in obese patients. The objective of this study was to establish, in a canine model, the influence of obesity on the clearance and steady-state volume of distribution of IVM, MOX, and a third analog, eprinomectin (EPR). An experimental model of obesity in dogs was based on a high calorie diet. IVM, MOX, and EPR were administered intravenously, in combination, to a single group of dogs in two circumstances, during a control period and when body weight had been increased by 50%. In obese dogs, clearance, expressed in absolute values (L/day), was not modified for MOX but was reduced for IVM and EPR, compared to the initial control state. However, when scaled by body weight (L/day/kg), plasma clearance was reduced by 55, 42, and 63%, for IVM, MOX and EPR, respectively. In contrast, the steady-state volume of distribution was markedly increased, in absolute values (L), by obesity. For IVM and MOX, this obese dog model suggests that the maintenance doses in the obese subject should be based on lean body weight rather than total weight. On the other hand, the loading dose, when required, should be based on the total body weight of the obese subject.

Theophylline Clearance in Obese Patients in Relation to Smoking and Congestive Heart Failure

1983 ◽  
Vol 17 (4) ◽  
pp. 274-276 ◽  
Author(s):  
Richard L. Slaughter ◽  
Robert A. Lanc
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Body Weight ◽  
Ideal Body Weight ◽  
Total Body Weight ◽  
Obese Patients ◽  
Ideal Body ◽  
Total Body ◽  
Nonobese Patients ◽  
Body Clearance

The effect of obesity on the total body clearance (Cltot) of theophylline was evaluated in nonsmokers and smokers with and without congestive heart failure (CHF). The obese patients were compared with similar nonobese subjects with regard to age, sex, and disease state. The total patient population numbered 150 adults. Cltot of theophylline, based on total body weight (TBW), averaged 0.60 ± 0.20 ml/min/kg in obese nonsmokers and did not differ from the nonobese, nonsmoking group. In obese nonsmoking patients with CHF, Cltot based on TBW was 0.40 ± 0.14 ml/min/kg, which was similar to Cltot values in nonsmoking CHF patients who were not obese. A trend toward a reduction in Cltot, based on TBW, as TBW increased, in nonsmoking patients with and without CHF, was observed. In contrast to the Cltot in nonsmokers, the Cltot of theophylline in obese smokers with and without CHF was similar to the Cltot values in nonobese populations only when based on ideal body weight. However, when compared with nonsmoking, nonobese patients, no differences were observed when Cltot was corrected for TBW. These findings suggest that theophylline maintenance dose can be based on TBW in obese patients who are smokers and nonsmokers (with and without CHF), using the average Cltot obtained for the nonsmoking patients with and without CHF.

scholarly journals Large Impact of obesity on the disposition of ivermectin, moxidectin and eprinomectin in a canine model: relevance for COVID-19 patients.

2021 ◽  
Author(s):  
Alain Bousquet-Melou ◽  
Anne Lespine ◽  
Jean-François Sutra ◽  
Isabelle Bargues ◽  
Pierre Louis Toutain
Keyword(s):  
Body Weight ◽  
Steady State ◽  
Obese Subject ◽  
Control Period ◽  
Total Body Weight ◽  
Canine Model ◽  
Volume Of Distribution ◽  
Lean Body Weight ◽  
Total Body

Background and Purpose: Based on in vitro data, ivermectin (IVM) has been proposed for the prevention and treatment of COVID-19, a condition for which obesity is a major risk factor. IVM dosage is based on total body weight and there are no recommendations to adjust dosage in obese patients. The objective of this study was to establish, in a canine model, the influence of obesity on the clearance and steady-state volume of distribution of IVM and two analog compounds, moxidectin (MOX) and eprinomectin (EPR). Experimental Approach: An experimental model of obesity in dogs was based on a high calorie diet. IVM, MOX and EPR were administered intravenously, simultaneously in combination, to a single group of dogs in two circumstances, during a control period and when body weight had been increased by 50%. Key Results: In obese dogs, clearance, expressed in absolute values (L/day), was not modified for MOX and reduced for IVM and EPR, compared to the initial control state. When scaled by body weight (L/day/kg), plasma clearance was reduced by 42, 55 and 63%, for MOX, IVM and EPR, respectively. In contrast, the steady-state volume of distribution was markedly increased in absolute values (L) by obesity. Conclusion and Implications: For IVM and MOX, the obese dog model suggests that the maintenance dose should not be adjusted by total body weight in the obese subject but should be based on lean body weight. On the other hand, the loading dose should be computed based on the total body weight of the obese subject.

scholarly journals Lean body weight versus total body weight to calculate the iodinated contrast media volume in abdominal CT: a randomised controlled trial

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Moreno Zanardo ◽  
Fabio Martino Doniselli ◽  
Anastassia Esseridou ◽  
Massimiliano Agrò ◽  
Nicol Antonina Rita Panarisi ◽  
...  
Keyword(s):  
Body Weight ◽  
Contrast Media ◽  
Controlled Trial ◽  
Total Body Weight ◽  
Lean Body Weight ◽  
Iodinated Contrast Media ◽  
Abdominal Ct ◽  
Iodinated Contrast ◽  
Significant Difference ◽  
Total Body

Abstract Objectives Iodinated contrast media (ICM) could be more appropriately dosed on patient lean body weight (LBW) than on total body weight (TBW). Methods After Ethics Committee approval, trial registration NCT03384979, patients aged ≥ 18 years scheduled for multiphasic abdominal CT were randomised for ICM dose to LBW group (0.63 gI/kg of LBW) or TBW group (0.44 gI/kg of TBW). Abdominal 64-row CT was performed using 120 kVp, 100–200 mAs, rotation time 0.5 s, pitch 1, Iopamidol (370 mgI/mL), and flow rate 3 mL/s. Levene, Mann–Whitney U, and χ2 tests were used. The primary endpoint was liver contrast enhancement (LCE). Results Of 335 enrolled patients, 17 were screening failures; 44 dropped out after randomisation; 274 patients were analysed (133 LBW group, 141 TBW group). The median age of LBW group (66 years) was slightly lower than that of TBW group (70 years). Although the median ICM-injected volume was comparable between groups, its variability was larger in the former (interquartile range 27 mL versus 21 mL, p = 0.01). The same was for unenhanced liver density (IQR 10 versus 7 HU) (p = 0.02). Median LCE was 40 (35–46) HU in the LBW group and 40 (35–44) HU in the TBW group, without significant difference for median (p = 0.41) and variability (p = 0.23). Suboptimal LCE (< 40 HU) was found in 64/133 (48%) patients in the LBW group and 69/141 (49%) in the TBW group, but no examination needed repeating. Conclusions The calculation of the ICM volume to be administered for abdominal CT based on the LBW does not imply a more consistent LCE.

Vancomycin volume of distribution estimation in adults with class III obesity

2019 ◽  
Author(s):  
Ryan D Dunn ◽  
Ryan L Crass ◽  
Joseph Hong ◽  
Manjunath P Pai ◽  
Lynne C Krop
Keyword(s):  
Body Weight ◽  
Total Body Weight ◽  
Volume Of Distribution ◽  
Patient Specific ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Parameter Estimates ◽  
Class Iii ◽  
Class Iii Obesity ◽  
Total Body

Abstract Purpose To compare methods of estimating vancomycin volume of distribution (V) in adults with class III obesity. Methods A retrospective, multicenter pharmacokinetic analysis of adults treated with vancomycin and monitored through measurement of peak and trough concentrations was performed. Individual pharmacokinetic parameter estimates were obtained via maximum a posteriori Bayesian analysis. The relationship between V and body weight was assessed using linear regression. Mean bias and root-mean-square error (RMSE) were calculated to assess the precision of multiple methods of estimating V. Results Of 241 patients included in the study sample, 159 (66.0%) had a BMI of 40.0–49.9 kg/m2, and 82 (34.0%) had a BMI of ≥50.0 kg/m2. The median (5th, 95th percentile) weight of patients was 136 (103, 204) kg, and baseline characteristics were similar between BMI groups. The mean ± S.D. V was lower in patients with a BMI of 40.0–49.9 kg/m2 than in those with a BMI of ≥50.0 kg/m2 (72.4 ± 19.6 L versus 79.3 ± 20.6 L, p = 0.009); however, body size poorly predicted V in regression analyses (R2 < 0.20). A fixed estimate of V (75 L) or use of 0.52 L/kg by total body weight yielded similar bias and error in this population. Conclusion Results of the largest analysis of vancomycin V in class III obesity to date indicated that use of a fixed V value (75 L) and use of a TBW-based estimate (0.52 L/kg) for estimation of vancomycin V in patients with a BMI of ≥40.0 kg/m2 have similar bias. Two postdistribution vancomycin concentrations are needed to accurately determine patient-specific pharmacokinetic parameters, estimate AUC, and improve the precision of vancomycin dosing in this patient population.

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