Infusion rates true steady-state

True steady state is usually only achieved for a prolonged period with intravenous infusion. If we assume that we wish for a similar steady value after oral administration, then we need to balance our dosing frequency with the rate of decline of drug concentration and the rule of thumb referred to earlier (dosing interval equal to drug half-life) can be applied. Unbound clearance and free drug are particularly applicable to drugs delivered by the oral route. For a well-absorbed compound the free plasma concentrations directly relate to Cli (intrinsic unbound clearance). 

Prior to the attainment of a true steady-state condition, the rate of infusion is always greater than the rate of elimination (i.e. Q>iCX) and only at true steady state does Q-KX. 

The true steady-state plasma concentration of a drug is constant for a given infusion rate and is obtained as time approaches infinity. We know, by definition, that when t = oo Cp = (Cp)ss- Hence, Eq. 10.3 takes the following form ... 

Please note that the time required to reach "practical" steady-state condition is always equal to 4.32ti/2 of that drug. For example, let us assume we wish to attain a plasma concentration of 10 pg mL at true steady state that is, the chosen infusion rate yields a true steady-state plasma concentration of 10pgmL . Therefore, lOpgmL X 0.95 = 9.5 pgmL is the "practical" steady-state concentration and it will occur at 4.32fi/2. 

Determine the infusion rate (Q) of procainamide hydrochloride required to attain the practical and true steady-state procainamide plasma concentrations, (Cp)ss, of 5.7 and 6.0pgmL , respectively. 

Determine the rate of elimination (KX) of procainamide at true steady-state condition and compare your answer with the chosen infusion rate. 

If it is desired to attain and then maintain the true steady-state procainamide plasma concentration (Cp)ss of 8mgL in this subject. In answering questions 5-8, make some important observations with regard to parameters that change as a result of change in the infusion rate and parameters that remain unaffected by it. 

Show the profile (rectilinear coordinates) of practical and true steady-state plasma concentrations against the infusion rate. 

Show the profile (rectilinear paper) of infusion rate necessary to attain a true steady-state plasma concentration against the systemic clearance or against the degree of renal impairment. 

Failure to change over to the second infusion rate will result in a procainamide plasma concentration of 16pgmL at true steady state. The therapeutic range for this drug is 4-8pgmL-. ... 

---