Loading dose of a drug depends upon
(a)Volume of distributionRef: Lippincott, 6th ed., pg. 21 and Katzung, 13th ed., pg. 50-51Sometimes rapid achievement of desired plasma concentrations of drugs is needed to produce the prompt response (e.g. in serious infections or arrhythmias). When the time to reach steady state is long, as it is for drugs with long half-lives and having high volume of distribution (Vd) due to their tissue affinities, it may be desirable to administer a large dose (loading dose) to achieve the desired plasma levels rapidly. The volume ot distribution is the proportionality factor that relates the total amount of drug in the body to the concentration in the plasma (Cp).LOADING DOSE= Vd X Desired steady state plasma concentrationLoading dose can be given as single dose or multiple doses over a short time. E.g. in case of treatment of AF by digoxin (longer acting drug with high Vd), loading dose is must to saturate the tissues and to achieve desired plasma concentration rapidly (otherwise it would take about a week for digoxin to achieve the steady state plasma concentration). Loading dose of Chloroquine is also required to treat the malaria.On the other hand, maintenance dose is dependent of the clearance (Cl) as we have to maintain the steady state concentration in view of the volume of the plasma cleared of drug per unit time. Hence, equation for maintenance dose isMAINTENANCE DOSE= Cl X Desired steady state plasma concentration
Volume of distribution
Clearance
Half life
bioavailability
General Pharmacology