Plasma concentration at time

FIGURE 3.2 Semilog plot of the plasma concentration, C, of a drug as a function of time, where Co is the projected plasma concentration at time zero and -1/2.303 is the slope of the elimination curve. 

Upon the administration of 1 gram of an aminoglycoside every 12 hours, the Cmj v, was found to be 8 mcg/mL. The plasma concentration at time zero was 63 mcg/mL and elimination rate constant was 0.14 hour 1. If it is desired to increase the Cmin ss to 10 mcg/mL, what should be the dose of the drug, and the new Cmax ss Assume that the drug follows linear kinetics. 

Cl plasma concentration at time zero fi/2a, distribution half-life f1/2jg, elimination half-life Kej, elimination rate constant from central compartment Ki2/.K2i, transfer rate constant between peripheral and central compartments AUC(o ), total area under plasma drug concentration time curve Vd(area> apparent volume of distribution GB, total body clearance. 

In this model, the drug concentration in the blood or plasma is proportional to both the concentration in other tissues (e.g. muscle) and to the total amount of drug in the body. When the equilibration of a drug between the central and peripheral compartments occurs less rapidly, relative to elimination, then the disposition kinetics of the drug can be described by assuming that there are two (or sometimes more) distribution compartments. The apparent varies with time after drug administration in these models because of the time required for equilibration between the compartments. Thus, for a two-compartment model, y,. is dose/(A + B), where A and B are the y intercepts (plasma concentrations at time 0) associated with the distribution and elimination phases, respectively. 

Figure 2.1 Slopes and y-axis intercepts for plots of an intravenous bolus of a one-compartment drug. (Cp)o, plasma concentration at time zero K, rate constant.

Equations for predicting the mass (amount) of drug and plasma concentration at time, t. 

The table indicates that if a drug is infused up to a time equal to one half life of the dmg, the plasma concentration at that time will always, under any condition in any subject for any dmg, represent 50% (/ = 0.5) of the tme steady-state concentration for the chosen infusion rate. If the dmg is infused up to two half lives, the plasma concentration will represent 75% of tme steady-state concentration ( = 0.75). If the infusion rate is doubled, the ratio of plasma concentration at time tto steady-state plasma concentration will remain unchanged. 

The loading dose is an intravenous bolus dose. However, in this instance, unlike the case of a single, isolated intravenous bolus dose considered in Ch. 3, the loading dose is immediately followed by the commencement of an intravenous infusion at constant rate. The intravenous bolus dose permits us to attain the desired plasma concentration at time = 0 and the concomitant constant infusion allows us to maintain this concentration. 

If the dosing interval is very long (greater than seven or eight half lives of a dmg, orinfinity), what will be the maximum and minimum plasma concentrations at time infinity following... 

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