Example: The average dose of cimetidine is 300 mg q 6 hr. The renal clearance of cimetidine is 75% of the total body clearance. What is the dose required in a patient with only 20% of the normal kidney function ? What will be the maximum and minimum conc achieved from the dose you recommended if cimetidine is rapidly absorbed ? (F = 0.6, Vd = 70 L, and the average half life 1.9 hr)

Kidney function
The decrease in kidney function results in
slower rate of cimetidine elimination and higher
steady state conc. Lower dose is needed in
patients with reduced kidney function.

Answer:

Dosefailure = Dosenormal [ 1-0.75(1-0.2) ]
Dosefailure = 120 mg q 6 hr
Kidney function
Cpmax =

F Dose

Vd (1 - e -k τ)

k is the rate constant during the reduced kidney function

Cpmin = Cpmax e -k τ
t1/2 failure =

1.9 hr

[1-0.75(1-0.2)] = 4.75 hr
kfailure =

0.693

4.75 hr = 0.146 hr -1
Cpmax =

(0.6) 120 mg

7L(1-e-0.146 hr -16hr) = 1.76 mg/L
Cpmin = 1.76 e-0.146 hr -16hr = 0.733 mg/L
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