Vancomycin pharmacokinetics in normal and morbidly obese subjects

Abstract

In an uncontrolled study, vancomycin pharmacokinetics were determined in four normal (total body weight [TBW], 65.9 to 89.1 kg) and six morbidly obese (TBW, 111.4 to 226.4 kg) subjects. The morbidly obese subjects were investigated 3 to 4 h after gastric bypass surgery. Mean terminal half-lives, volumes of distribution, and total body clearances for the normal controls and the morbidly obese subjects were 4.8 h, 0.39 liter/kg, and 1.085 ml/min per kg versus 3.2 h, 0.26 liter/kg TBW, and 1.112 ml/min per kg TBW. The mean terminal half-life and volume of distribution values were significantly different between the two groups. Strong correlations were found between TBW and both volume of distribution (correlation coefficient, 0.943) and total body clearance (correlation coefficient, 0.981). These results implied that TBW should be used to calculate vancomycin doses for morbidly obese patients. This was supported by the finding that there was no significant difference in the daily dose (in milligrams per kilogram per day) required to produce an average steady-state concentration of 15 ,ug/ml in the two groups (23.4 ± 1.5 mg/kg per day for normal weight subjects and 24.0 ± 3.4 mg/kg per day TBW for the postsurgery morbidly obese subjects). Therefore, the morbidly obese required higher total doses (in milligrams per day) than did normal weight subjects to achieve the same mean steady-state concentrations. In addition, normal weight and morbidly obese subjects had similar volumes of the central compartment (7.7 and 6.4 liters, respectively). To avoid high transient peak concentrations which could occur when obese patients are given larger total doses (in milligrams per day), maintenance doses may be given at more frequent intervals. The shorter mean terminal half-lives observed in morbidly obese patients allows more frequent dosing without excessive accumulation.

Challenges of Treating a 466-Kilogram Man With Acute Kidney Injury

“…Unfortunately, few anti-microbial or other drug dosing guidelines exist for moderately obese individuals, much less for those with super obesity (8). Our patient's vancomycin volume of distribution (131.1 L) was somewhat lower than the urea volume of distribution as calculated using the conventional total body water (0.6 * weight(kg)), Watson (9), or Hume-Meyer formulas (10), though it was consistent with previous findings in obese subjects (11)(12)(13). This discrepancy highlights the limitations of available formulas and suggests that drug dosing strategies may not be substantially different between the obese and super obese.…”

Analytical methods for vancomycin determination in biological fluids and in pharmaceuticals

“…The RIA method [34][35][36][37] had also been employed. Despite the good quality of the analytical results, it is less efficient and more expensive than FPIA, and there is also the disadvantage of using radioactive substances 37 .…”

Initial Vancomycin Dosing Recommendations for Critically Ill Patients Undergoing Continuous Venovenous Hemodialysis

“…[42][43][44] del Mar Fernández and others 44 observed that the mean volume of distribution of vancomycin among 46 critically ill patients was 1.69 L/kg, nearly double that observed in healthy adult subjects with normal renal function (0.4-1 L/kg). 30,[45][46][47] In a population-based = area under the concentration-time curve over 24 h, MIC = minimum inhibitory concentration. *MIC was assumed to have a normal distribution, with a range between 0.5 and 2 mg/L and a mean value of 1 mg/L, with 1 million iterations using Monte Carlo simulation.…”