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With permission from Springer Verlag. aAxline and Simon.44 bMcCracken and Jones.45

With permission from Springer Verlag. aAxline and Simon.44 bMcCracken and Jones.45

important because binding to plasma proteins results in a reduction in the free (unbound) drug concentration in plasma, and, consequently, the apparent volume of distribution increases in direct proportion to the extent of binding. Since the half-life of drug elimination increases with the volume of distribution, the time of elimination is also lengthened.

The combined effects of variation in protein binding and in renal elimination for drugs eliminated solely by glomerular filtration and exhibiting various degrees of binding can be computed by the mathematical model described by Keen.48 The computed estimates for newborn infants and adults are compared in Table 4.5. These estimates show the multiple, F, by which plasma protein binding would increase the elimination half-life, assuming the initial free drug concentration is the same for newborns and adults.

Table 4.5 shows the greatest potential effect of protein binding on elimination half-life in both newborns and adults occurs for a drug confined to plasma water. For a highly bound drug (90% or more), there is at least a 10-fold increase in elimination half-life. The increase is the same in both age groups because the plasma water space, about 4-5% of the body weight, is the same in both groups. In contrast, when the drug is distributed in extracellular water, or total body water, plasma binding has smaller effects on the rate of drug elimination. In newborns,

Table 4.5 The Potential Effect of Plasma Protein Binding on Time of Drug Elimination in Newborns versus Adults after a Single Dose of Drugs Excreted by Glomerular Filtration3

Plasma protein

Drug distributed in

Plasma water

Extracellular water

Total body water

Plasma protein

Plasma water

Extracellular water

Total body water

(% bound)

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