THE GENERAL IMPACT OF OBESITY Clause Samples

THE GENERAL IMPACT OF OBESITY. ON THE PHARMACOKINETICS OF DRUGS The pharmacokinetics of a specific drug depend on the physiochemical properties of that drug and the biological environment of the patient. The independent pharmacokinetic parameters: volume of distribution (Vd) and total clearance (CL) determine the drug elimination half-life (t1/2), which, in turn, determines the maintenance dose for that drug. (▇▇▇▇▇▇ et al., 2010) The Vd describes the extent to which a drug distributes into extravascular tissues and is dependent on the physiochemical properties of that drug. (▇▇▇▇▇ et al., 2011) Drug clearance is determined by hepatic and renal physiology, which are both influenced by body weight. Certain metabolic processes may be more active in obese patients, such as glucoronidation, sulphation, increased cytochrome P450-2E1 activity and phase II conjugation, resulting in increased drug clearance. Additionally, non-diabetic obese patients have been shown to have increased glomerular filtration as a result of structural renal changes and increased renal plasma flow, resulting in increased renal clearance. (▇▇▇▇▇▇▇ et al., 2000) However, one study suggests that obesity-related liver lipodystrophy may result in hepatic dysfunction, thus, decreased drug clearance. (▇▇▇▇▇▇ et al., 2010) The main factors which affect the tissue distribution of drugs are: body composition, regional blood flow and the affinity of the drug for plasma proteins and/or tissue components. (▇▇▇▇▇▇ et al., 2010) Obese individuals have a lower cardiac output and decreased blood supply to the adipose tissue. There are uncertain differences in drug plasma protein binding with reports of increased binding to alpha-1 acid glycoprotein in obese patients. (▇▇▇▇▇▇▇ et al., 1983) Obese individuals have an increased percentage of fat per kilogram of total body weight and decreased lean tissue compared to normally-weighted individuals of the same age, height and gender. (▇▇▇▇▇▇▇, 2000) ▇▇▇ explains that since 99% of the body’s metabolic processes occur within lean tissues. It is this compartment which should be used when quantifying changes in clearance for individuals of all body weights. Han and colleagues critically evaluated drug dosing in obesity, making three crucial observations: absolute drug clearance is greater in obese individuals; clearance increases non-linearly with weight; and clearance correlates linearly with lean body weight. (Han et al., 2007) Lean body weight closely represents fat free mass, which has bee...