Drug distribution , volume obesity

Volume of distribution is commonly calculated for a particular patient using body weight (70 kg body weight is assumed for the values in Table 3-1). If a patient is obese, drugs that do not readily penetrate fat (eg, gentamicin and digoxin) should have their volumes calculated from ideal body... 

A review of the effects of obesity on drug pharmacokinetics briefly mentioned that the steady-state volume of distribution of lithium correlated with ideal body weight and fat-free mass but not with total body weight (514). Lithium clearance was greater in those with obesity than in lean controls, suggesting that obese patients may require larger maintenance doses to maintain target serum concentrations. 

Phenytoin enters the brain rapidly and is redistributed to other body tissues, including breast miUc and the placenta. It is highly (>90%) protein bound. Phenytoin competes for albumin sites with other highly protein bound drugs. It is essential to know the patient s serum albumin level in interpreting the serum concentrations of phenytoin. Patients with significant renal dysfunction will have altered phenytoin protein binding. Obesity increases the volume of distribution of phenytoin. 

Cheymol G, Poirier J-M, Carrupt PA, Testa B, Weissenburger J, Levron J-C and Snoeck E., Pharmacokinetics of p-adrenoceptor blockers in obese and normal volunteers, Br. J. Clin. Pharmacol., 43, 563-570 (1997). NB Determined by extrapolation from MeOH-water solutions, using the Yasuda-Shedlovsky procedure. Cited in Lombardo F, Obach RS, Shalaeva MY and Gao F, Prediction of human volume of distribution values for neutral and basic drugs. 2. Extended data set and leave-class-out statistics, /. Med. Chem., 47, 1242-1250 (2004) ref. 14. 

The volume of distribution (VD) of many drugs is increased in patients with moderate to severe CKD as well as in those with pre-existing CKD who develop AKI the increase in VD may be the result of decreased protein binding or fluid overload obese CKD and AKI patients and those with large variations in serum protein levels should have their drug dosage individualized... 

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