a Values tabulated were calculated assuming a single dose of drug gives a blood level of 100 units and is eliminated by a first-order process. For a first-order process with a rate constant k (time-1)
where a = amount of drug present at time zero, x = amount gone after time t, and a — x = amount remaining after time t. It can be shown that ti/2 = 2.303 log 2/k
If we set a = 1, then ti/2 = — log(1 — x)/0.301
where (1 — x) is the fraction of drug remaining. Also, since dose (here 100) = (fraction drug gone at t), then the maximum drug level= 100/x and the variation in blood level is
when the drug is given at intervals of time t. F is the factor by which plasma binding decreases the maximum blood level assuming the initial free drug concentration is the same in each case, as described in Table 4.5.
plasma protein binding exerts smaller effects on maximum and minimum drug levels.
In healthy, elderly persons, age-dependent changes in plasma protein binding are generally not clinically relevant because drug elimination increases when the free (unbound) drug concentration is enhanced.22 A decrease in plasma protein binding may thus obscure an age-related decrease in drug clearance.8 Acidic drugs, such as diazepam, phenytoin, warfarin, and salicylic acid, bind principally to albumin, whereas basic drugs such as lignocaine and propanolol bind to aj-acid glycoprotein. However, neither of these proteins has been observed to exhibit substantial changes in their concentrations in elderly persons.18
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