Drug Pharmacokinetics in the Postoperative Period

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Abstract

Summary

Marked changes in physiological function and in the metabolism of endogenous substances take place after trauma and operation, and these may influence the pharmacokinetics of drugs. Increased secretion of hormones, such as hydrocortisone and glucagon occurs. The liver blood flow increases, whereas gastrointestinal motility decreases. There is a tendency to hyperglycaemia, and fat is mobilised from the body stores. During the first few days after operation there is increased protein breakdown, and the plasma concentration of albumin is reduced for 10 to 14 days.

To date, few investigations have been performed to elucidate the pharmacokinetic consequences of these physiological changes, but it is apparent that altered disposition of drugs can occur. The absorption of some orally administered drugs may well be altered during the early postoperative period owing to decreased gastrointestinal motility. The degree of plasma protein binding of phenytoin and quinidine has been found to be modified after surgery, mostly due to altered concentration of plasma proteins. Although this is probably compensated by changes in distribution and elimination of the drug. it is conceivable that high unbound drug concentrations may be achieved temporarily. Many factors apparently accelerate the elimination of drugs after operation. Liver blood flow increases, plasma protein binding of acidic drugs diminishes, and further, the drug metabolising enzyme activity of the liver has been found to increase. The elimination rate of antipyrine is increased after surgery, and is thought to be due to acceleration of the metabolism of the drug. The increase in enzyme activity may be explained by the altered secretion of hormones, but may also be due to the concomitant use of other drugs.

The use of drugs in relation to surgery is important. Further investigation to elucidate their pharmacokinetics in the postoperative period is clearly necessary in order to establish safe and effective therapy.

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