Atracurium, pharmacokinetics and metabolites

The pharmacology applicable to anaesthetic practice is often different from that of other specialities. The drugs used are different, a short duration of action is desired to increase flexibility and toxicity is not an overwhelming concern because of the short duration of exposure. Thus, recent drug development has focused on short-acting agents. This trend has been noticed with inhalational agents, narcotics, benzodiazepines, local anaesthetics and beta blockers. This is in contrast to the trend in other specialities. For example, different needs prompted cardiologists to abandon propranolol for the longer-acting nadolol and atenalol, while anaesthetists are starting to use the shorter-acting esmolol. This tendency to use short-acting drugs carries the problem of what happens to them. Most drugs are excreted in the urine or the bile or are metabolized, usually in the liver. Thus, kidney and/or liver function is necessary for their disposition. Unfortunately, these organs have limited capacity, considering the short duration of action which we want. The glomeruli in the kidney can filter 1-2 ml. min -j of plasma per kg body weight. In the absence of tubular secretion or reabsorption, the clearance (CI) of a drug totally excreted via the kidney is approximately 1-2 ml .kg -~ min -~ . Then, the elimination half-life (hiS) is directly proportional to the volume of distribution (Vd), according to the formula: ~