Aminoglycoside dosing weight correction factors for patients of various body sizes

Abstract

Prior investigations have suggested the use of a dosing weight correction factor of ideal body weight (IBW) plus 40% excess body weight (EBW, where EBW ‫؍‬ total body weight [TBW] ؊ IBW) to determine the weight to use for aminoglycoside dosing in morbidly obese (TBW/IBW ratio, >2) patients. Little data are available to provide dosing information for underweight or moderately obese patients. We investigated aminoglycoside pharmacokinetics in 1,708 patients receiving gentamicin and tobramycin. Patients were stratified into underaverage-weight or overweight weight categories based on both TBW/IBW ratio and body mass index (weight/ height 2 ratio), which has been shown to correlate with physiologic estimates of body fat. Regression analyses revealed that the TBW/IBW ratio predicts the volume of distribution. Dosing weight correction factors to give equivalent predicted peak aminoglycoside concentrations with a 2-mg/kg loading dose are 1.13 times the TBW for underweight patients and 0.43 times the EBW plus IBW for overweight patients. There were no large differences between the dosing weight correction factors derived from IBW-and body mass index-based classification systems. These data generate useful aminoglycoside dosing weight equations for both underweight and overweight patients.Ascertainment of accurate pharmacokinetic parameters for aminoglycoside dosing remains critical, as the serum drug concentration relates directly to both therapeutic response and toxic effect. Both maximum 1-h postinfusion peak and overall mean peak serum drug concentrations have been identified as significant predictors of therapeutic success for treatment of gram-negative bacteremia and pneumonia (16,17). Moore et al. demonstrated a linear dose-response effect correlating the ratio of peak serum aminoglycoside concentration/MIC to clinical response in treatment of a broad array of documented gram-negative infections (15). Deziel-Evans et al. also noted that this ratio served as an accurate determinant of response in patients treated with aminoglycosides (10). Conversely, inadequate serum drug concentrations may result in treatment failure (16,17). In addition, the narrow therapeutic effect/toxicity ratio for aminoglycosides mandates accuracy in predicting dosing parameters when attempting to reduce the risk of nephrotoxicity (4).The physiologically linked variable volume of distribution at steady state (V ss ) is an important determinant of serum drug concentration. However, V ss remains a poorly predicted pharmacokinetic parameter affecting aminoglycoside dosing in morbidly obese patients (TBW/IBW ratio Ͼ2, where TBW is total body weight and IBW is ideal body weight). This is due, in part, to the variable penetration of these highly polar polycationic compounds into adipose tissue. Additional factors influencing estimations of V ss in the population include increased projections of lean body mass and blood volume, as well as organ hypertrophy (2, 12).Past investigators have utilized dosing weight correction factors (DWCFs) to normali...

Soft tissue concentrations of ciprofloxacin in obese and lean subjects following weight-adjusted dosing

“…12 ± 16 Despite considerable variability among the various study populations, consensus dosing weight correction factors (DWCF) for aminoglycosides of 40% of excess body weight (EBW, EBW TBW-IBW) IBW are accepted by most clinicians. 12 Similar DWCF have been proposed for cipro¯oxacin. Allard et al measured cipro¯oxacin plasma concentrations after a dose of 400 mg in obese and normal subjects.…”

Bedside Estimation of Patient Height for Calculating Ideal Body Weight in the Emergency Department

“…Ventilator volume settings calculated using actual weight, particularly in obese patients, can result in excess ventilatory volumes, barotrauma, and hemody-namic compromise (1). Although most medications are dosed using actual, true body weight, some medications are best dosed using IBW, or a combination of IBW and actual body weight, particularly in obese patients (2)(3)(4). Although drug dosing and ventilator volume settings initiated in the ED are based on preliminary estimates and later adjusted based on the patient's response, the goal should always be to initiate drug dosing and ventilatory settings as close as possible to the patient's physiological requirements.…”

“…A validation set (102 patients) then compared the accuracy of IBW using true height calculated from the regression formula vs. IBW using gold-standard true height. Regression formula for men tibial length-IBW (kg) ‫؍‬ 25.83 ؉ 1.11 ؋ tibial length; for women tibial length-IBW ‫؍‬ 7.90 ؉ 1.20 ؋ tibial length; R 2 …”

Drug disposition in obesity and protein–energy malnutrition

“…It has been suggested that loading doses of aminoglycosides be increased by a factor of 1 . 1 in underweight patients (74) . Drug clearance is also reduced in PCM for chloramphenicol, penicillin, quinine and isoniazid (51,53,(75)(76)(77)(78) .…”

“…The mg/kg dosing of these drugs should then be based on an Adj-BW using a correction factor of 0 . 4 to represent the proportion of the excess body weight into which the aminoglycosides distribute (74,81) . There is very little data on the antifungal agents, but dosing based on BWt has been suggested for amphotericin as both Vd and clearance may be increased in obesity (82)(83)(84) .…”