Loading dose calculation

When intermittent doses are given, the loading dose calculated from equation (12) will only reach the average steady-state concentration and will not match the peak steady-state concentration (Figure 3-6). To match the peak steady-state concentration, the loading dose can be calculated from equation (13) ... 

To avoid toxicity, half of the loading dose (calculated or on a mg/kg basis) is nsually administered at a rate <50 mg/min followed by the remaining dose divided in equal parts at 5-min intervals (see example below). The usual maximum total dose is 300 mg. ... 

The calculated peak concentration is not always the measured concentration. For bi-exponential kinetics the calculated peak concentration is less, but after oral dosing, the calculated peak concentration is higher than the highest measurable plasma concentration. The peak concentration provides a target for the loading dose to start with (Dload). 

A loading dose that produces a of 35 pg/mL is desired, and this can be calculated as follows [from Eq. (16)] ... 

The maintenance dose may be defined as the size of the dose required to maintain the therapeutic range according to the dosage regimen. The maintenance dose needed to replace the amount lost over the dosing interval is the difference between the loading dose and the amount remaining at the end of the interval. It is calculated as,... 

Using a simple one-compartment model, the loading dose and the infusion rate required to maintain a constant plasma concentration can be calculated as follows. 

The units of volume of distribution are those of volume (i.e. litres) and can be adjusted for, say, body weight. The two main uses of volume of distribution are in the calculation of loading doses for rapid onset of drug effect, and in understanding changes in half-life (see below). 

If rapid digitalization is considered medically appropriate, it may be achieved by administering a loading dose based upon projected peak digoxin body stores. Calculate maintenance dose as a percentage of the... 

If the patient s clinical response necessitates a change from the calculated loading dose of digoxin, then base calculation of the maintenance dose upon the amount actually given. 

The principle that emerges from these three examples is a simple one. The only factors important in calculating an intravenous loading dose of a drug are the desired plasma concentration and the apparent volume of distribution. Other kinetic parameters do not come into this very straightforward calculation. 

For the theophylline example given in Example Maintenance Dose Calculation, the loading dose would be 350 mg (35 L x 10 mg/L) for a 70-kg person. For most drugs, the loading dose can be given as a single dose by the chosen route of administration. 

Give a loading dose or maintenance dose calculated from TC, Vd, and CL. 

Ethanol Methanol, ethylene glycol Ethanol therapy can be started before laboratory diagnosis is confirmed. A loading dose is calculated so as to give a blood level of at least 100 mg/dL (42 g/70 kg in adults). 

Vi most likely would be used when calculating a loading dose for a drug exhibiting two-compartment behavior. V2 is almost never used in the determination of dosing but sometimes may be used in blood protein or tissue-binding calculations and in the estimation of Vd ss. 

Volume of distribution (V) is the apparent volume that relates the amount of drug in the body (A) to the measured concentration (C). It is often used to calculate a loading dose. 

FIGURE 2.5 Siimilation of plasma (solid line) and tissue (heavy dashed line) digoxin concentrations after intravenous administration of a 0.75-mg loading dose to a 70-kg patient with normal renal function. Cq is estimated by back extrapolation (dotted line) of elimination-phase plasma concentrations. is calculated by dividing the administered drug dose by this estimate of Cq, as shown. Tissue concentrations are referenced to the apparent distribution volume of a peripheral compartment that represents tissue distribution. (Reproduced with permission from Atkinson AJ Jr, Kushner W. Annu Rev Pharmacol Toxicol 1979 19 105-27.)... 

The volume of distribution is a proportionality constant that relates the amount of drug in the body to the serum concentration. The volume of distribution is used to calculate the loading dose of a drug that will immediately achieve a desired steady-state concentration. The value of the volume of distribution is determined by the physiologic volume of blood and tissues and how the drug binds in blood and tissues. 

---