Multiple dosing Extravascular Administration Dr Mohammad Issa Saleh

Multiple dosing: Extravascular Administration Dr Mohammad Issa Saleh

Multiple dosing: Extravascular Administration

Multiple dosing: Extravascular Administration n Concentration after n doses: n Concentration at steady state n: number of doses, T: dosing interval

Multiple dosing: Extravascular Administration n Time to get to maximum conc after n doses: n Time to get to maximum conc at steady state:

Accumulation ratio n Accumulation can be determined by comparing the minimum plasma concentrations of drug at steady state and following the first dose:

Accumulation ratio n If the dose was administered in the elimination phase (no significant absorption occurs, accumulation ratio can be simplified into:

Time to reach steady state conc. n Fraction of steady state conc obtained after the nth dose is given by: n At very large values of Ka (i. e. Ka/K≥ 10), time to get to steady state can be represented as:

The AUC during a dosing interval at steady state is equal to the total AUC following a single dose (For linear PK)

Average steady state conc n The ‘‘average’’ plasma concentration of a drug at steady state for extravascularly administered dose can be calculated from:

Example 1 n QJ is a 67 -year-old, 80 -kg male being treated for chronic obstructive pulmonary disease. Sustained-release oral theophylline is being added to his drug regimen. Assuming F = 1. 0, V = 40 L, and t 1/2 = 5 hours, compute an oral theophylline dose to be administered every 12 hours that would achieve a Css = 8 mg/L using the average steady-state concentration equation

Example 2 n A patient is taking 1000 mg sulfamethoxazole tablet every 12 hours for the treatment of urinary tract infection. Sulfamethoxazole is rapidly and completely absorbed after oral administration. What is the amount of sulfamethoxazole eliminated during one dosing interval at steady state ? Solution: amount eliminated during one dosing interval at steady state = amount administered during one dosing interval at steady state = maintenance dose= 1000 mg

Example 3 n During repeated administration of 60 mg indomethacin tablet every 12 hours (F=1) for the treatment of rheumatoid arthritis the AUC during one dosing interval was 8 mg-hr/L. What is the average indomethacin steady state plasma concentration during this dosing regimen (60 mg every 12 hours) ?

Example 4 n JB is a 78 -year-old, 100 -kg male being treated with digoxin for heart failure. While receiving digoxin tablets 125 μg daily, an average steadystate digoxin concentration equal to 0. 6 μg/L is obtained. Assuming F = 0. 7, ¨ Compute digoxin clearance for the patient using the average steady-state concentration equation. ¨ Compute a new digoxin tablet dose for the patient that will achieve Css = 1. 2 μg/L. .

Example 4 1. Calculate clearance (Cl): At steady state: input rate = output rate dosing rate = elimination rate

Example 4 2 - Calculate a new dose patient that will achieve Css = 1. 2 μg/L: 0. 6 µg/L 125 µg 1. 2 µg /L ? ? µg