The Influence of Renal Function on the Pharmacokinetics and Pharmacodynamics and Simulated Time Course of Doxacurium

Fisher, Dennis M.; Reynolds, Kellie S.; Schmith, Virginia D.; Hsu, James; Sokoll, Martin D.; Lennon, Robert L.; Caldwell, James E.

doi:10.1097/00000539-199909000-00049

Cited by 3 publications

(1 citation statement)

References 10 publications

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“…Fisher et al [93] assessed the role of several covariates, including obesity, on the pharmacokinetic and pharmacodynamic profiles of doxacurium, a long-acting nondepolarizing muscle relaxant. They showed that obesity decreased both doxacurium's clearance (1.1% per percentage above IBW) and its neuromuscular junction sensitivity (0.4% per percentage above IBW).…”

Section: Muscle Relaxantsmentioning

confidence: 99%

Anesthesia in the obese patient: Pharmacokinetic considerations

Casati

Putzu

2005

Journal of Clinical Anesthesia

179

128

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Section: Muscle Relaxantsmentioning

confidence: 99%

Anesthesia in the obese patient: Pharmacokinetic considerations

Casati

Putzu

2005

Journal of Clinical Anesthesia

179

128

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What is the best size descriptor to use for pharmacokinetic studies in the obese?

Green

Duffull

2004

Brit J Clinical Pharma

312

243

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The prevalence of obesity in the western world is dramatically rising, with many of these individuals requiring therapeutic intervention for a variety of disease states. Despite the growing prevalence of obesity there is a paucity of information describing how doses should be adjusted, or indeed whether they need to be adjusted, in the clinical setting. This review is aimed at identifying which descriptors of body size provide the most information about the relationship between dose and concentration in the obese. The size descriptors, weight, lean body weight, ideal body weight, body surface area, body mass index, fat-free mass, percent ideal body weight, adjusted body weight and predicted normal body weight were considered as potential size descriptors. We conducted an extensive review of the literature to identify studies that have assessed the quantitative relationship between the parameters clearance (CL) and volume of distribution ( V ) and these descriptors of body size. Surprisingly few studies have addressed the relationship between obesity and CL or V in a quantitative manner. Despite the lack of studies there were consistent findings: (i) most studies found total body weight to be the best descriptor of V . A further analysis of the studies that have addressed V found that total body weight or another descriptor that incorporated fat mass was the preferred descriptor for drugs that have high lipophilicity; (ii) in contrast, CL was best described by lean body mass and no apparent relationship between lipophilicity or clearance mechanism and preference for body size descriptor was found. In conclusion, no single descriptor described the influence of body size on both CL and V equally well. For drugs that are dosed chronically, and therefore CL is of primary concern, dosing for obese patients should not be based on their total weight. If a weight-based dose individualization is required then we would suggest that chronic drug dosing in the obese subject should be based on lean body weight, at least until a more robust size descriptor becomes available.

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