Choosing a loading dose

For a given drug, an average of four to five half-lives are required to reach therapeutic plasma concentrations. Loading doses are used routinely to provide rapid induction and achieve adequate therapeutic plasma concentrations in a short time, assuming that this is clinically feasible. The loading dose in patients with renal failure is usually no different from that in patients with normal renal function ( Bennettefal 1994).

Half-life

Half-life is defined as the time required for the plasma drug concentration to decrease to 50 per cent of its original concentration. Drug half-life is a simple concept and is most commonly utilized to estimate the time to achieve steady state plasma concentrations ( Rudyand Brat,e.rJ994). However, it is frequently misunderstood. The half-life of a drug does not explain solely the drug excretion process; in contrast, it is a by-product of drug distribution and clearance (metabolism and excretion). In patients with renal failure, the half-life and the time to reach steady state are usually prolonged. If doses remain unchanged, the steady state plasma concentration in a patient with renal failure state will be higher than that in a patient with normal renal function. A loading dose is usually given, if feasible, to reduce the time required to achieve a therapeutic plasma concentration. Reduction of the total dose (by decreasing the dose or extending the dosing interval) will avoid higher steady state plasma concentrations (Rudy.and Bra.t§rJ9.94).

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