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Interrelationship Between Renal Haemodynamics, Drug Kinetics and Drug Action

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Summary

The renal haemodynamics of a particular patient may affect the pharmacological and pharmacokinetic properties of various drugs. For example, diminution in renal haemodynamics may lead to fluid retention and an increase in the volume of distribution of the drug. Also, fluid retention causes a decrease in plasma protein concentration which for certain drugs can result in altered protein binding and consequently increased proportion of unbound drug and a more marked pharmacological response.

The clearance of many drugs and/or metabolites also in influenced by the stale of renal haemodynamics. In states of poor renal perfusion, drugs which are mainly eliminated through renal mechanisms have a reduced rate of clearance. The resultant prolongation of the elimination half-life of the drug may increase its toxicity. Knowledge of the renal haemodynamic state, therefore, should be considered in determining the dose and frequency of drug administration.

Studies in man have shown that both renal blood flow and glomerular filtration rate are reduced below normal in states of congestive heart failure, liver disorders such as cirrhosis, and, of course, acute and chronic renal failure. In these pathological states, severe cortical vasoconstriction may be present and primarily account for the impairment in renal haemodynamics and alterations in drug kinetics and action.

Not only can the renal haemodynamic state affect the actions of drugs, but also exogenous administration of certain drugs can alter renal haemodynamics. The kidney’s response to these agents is influenced by pathological and physiological factors, including sodium balance and the ability of the kidney to autoregulate its blood flow. In general, however, renal haemodynamics are diminished by renal vasoconstrictors and improved by renal vasodilators. The altered state of renal haemodynamics in turn may modify the pharmacological and pharmacokinetic properties of other drugs present in the body.

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Authors and Affiliations

  1. Squibb Institute for Medical Research, Princeton, New Jersey, 08540, USA

    Kenneth L. Duchin

  2. Medicine/Renal, University of Colorado Medical Center, Box C281, 4200 East Ninth Avenue, Denver, Colorado, 80262, USA

    Robert W. Schrier

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  1. Kenneth L. Duchin
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  2. Robert W. Schrier
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Duchin, K.L., Schrier, R.W. Interrelationship Between Renal Haemodynamics, Drug Kinetics and Drug Action. Clin Pharmacokinet 3, 58–71 (1978). https://doi.org/10.2165/00003088-197803010-00004

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