Choosing the right nonsteroidal anti-inflammatory drug for the right patient - A pharmacokinetic approach

(NSAIDs), a group that has recently been augmented by the introduction of t he selective cyclo-oxygenase-2 inhibitors, requires adequate knowledge of t heir pharmacokinetics. After oral administration, the absorption of NSAIDs is generally rapid and complete. NSAIDs are highly bound to plasma proteins, specifically to album in (>90%). The volume of distribution of NSAIDs is low, ranging from 0.1 to 0.3 L/kg, suggesting minimal tissue binding. NSAID binding in plasma can b e saturated when the concentration of the NSAID exceeds that of albumin. Most NSAIDs are metabolised by the liver, with subsequent excretion into ur ine or bile. Enterohepatic recirculation occurs when a significant amount o f an NSAID or its conjugated metabolites are excreted into the bile and the n reabsorbed in the distal intestine. NSAID elimination is not dependent on hepatic blood flow. Hepatic NSAID elimination is dependent on the free fra ction of NSAID within the plasma and the intrinsic enzyme activities of the Liver. Renal elimination is not an important elimination pathway for NSAID s, except for azapropazone. The plasma half-life of NSAIDs ranges from 0.25 to >70 hours, indicating wide differences in clearance rates. Hepatic or r enal disease can alter NSAID protein binding and metabolism. Some NSAIDs wi th elimination predominantly via acylglucuronidation can have significantly altered disposition. Pharmacokinetics are also influenced by chronobiology , and many NSAIDs exhibit stereoselectivity. There appear to be relationships between NSAID concentration and effects. A t therapeutically equivalent doses, NSAIDs appear to be equally efficacious . The major differences between NSAIDs are their therapeutic half-lives and safety profiles. NSAIDs undergo drug interactions through protein binding displacement and competition for active renal tubular secretion with other organic acids. When choosing the right NSAID for the right patient, individual patient-spe cific and NSAID-specific pharmacokinetic principles should be considered.