Pharmacokinetics of Drugs in Obesity

Pharmacokinetic data in obesity are only available for a limited number of drugs. The rate or extent of drug absorption is not known to be altered by obesity which is not complicated by other medical disease. In contrast, drug distribution is in some instances significantly altered in obesity. Digoxin and bromsulphalein, both hydrophilic drugs, do not distribute into excess bodyweight over ideal bodyweight. However, antipyrine, paracetamol, aminoglycoside antibiotics and theophylline, all of intermediate lipid solubility, distribute to a limited extent into excess bodyweight over ideal bodyweight, although not as extensively as into ideal bodyweight. Benzodiazepines, halothane and enflurane, highly lipophilic agents, may distribute much more extensively into excess bodyweight over ideal bodyweight than into ideal bodyweight. This suggests some relationship between drug distribution and drug lipid-solubility in obese subjects. Whether these distributional changes in obesity will hold for other drugs is not currently known. Drug protein binding has not been demonstrated to be changed in obesity, data being presently available only for the basic drugs diazepam and desmethyldiazepam. Drug biotransformation in obesity is unchanged for oxidatively metabolised drus studied to date. Paracetamol, the only metabolised drug which is conjugated for which pharmacokinetic parameters have been accurately determined in obesity, undergoes increased clearance in obese subjects.