Influence of Race or Ethnicity on Pharmacokinetics of Drugs

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Abstract
Review of the current literature on racial differences in pharmacokinetics of drugs supports the premise that only pharmacokinetic processes which are biologically or biochemically mediated have the potential to exhibit differences between racial or ethnic groups. Thus, the pharmacokinetic factors which can be expected to potentially exhibit racial differences are (1) bioavailability for drugs which undergo gut or hepatic first-pass metabolism, (2) protein binding, (3) volume of distribution, (4) hepatic metabolism, and (5) renal tubular secretion. Absorption (unless active), filtration at the glomerulus, and passive tubular reabsorption would not be expected to exhibit racial differences. As is evident from this review, there are relatively few drugs for which there is information on ethnic or racial differences in pharmacokinetics. Thus it is often necessary to try to predict whether such differences might exist. Taking into consideration the above factors and evaluation of the pharmacokinetic characteristics of the drug, it should be possible to identify those drugs most likely to exhibit differences in their pharmacokinetics. For example, a drug which is eliminated entirely by the kidneys through filtration and reabsorption and is not highly bound to plasma proteins (or is bound to albumin) is highly unlikely to exhibit racial differences in its kinetics. Conversely, a drug which undergoes significant gut and/or hepatic first-pass metabolism and is highly bound to AGP is much more likely to exhibit kinetic differences between racial groups. A discussion of the impact of racial differences in kinetics on drug response or racial differences in drug efficacy, toxicity, or pharmacodynamics (concentration-response relationship) is beyond the scope of this review. However, a number of the papers described above also evaluated differences in pharmacodynamics or response. Among the comparisons of Chinese and Caucasians, these include the papers on propranolol, morphine, nifedipine, triazolam, diazepam, and omeprazole. For those studies comparing differences in blacks and Caucasians, responses or pharmacodynamics were also determined in the studies of propranolol, trimazosin, and methylprednisolone. Interested readers are also referred to the review by Wood and a more recent review by Kitler for additional discussion of ethnic/racial differences in pharmacodynamics/drug response.