Example: Codeine is metabolized to several metabolites including 0-demethylation to morphine which requires CYP2D6. About 3-10% of the total population have lower than normal CYP2D6 level. Calculate the steady state morphine/codeine conc ratio during repeated codeine administration in patients with normal and abnormal CYP2D6 levels assuming that CYP2D6 level affects the fraction of codeine dose convened to morphine (fm = 0.1 in normal and 0.05 in abnormal CYP2D6 patients) and does not affect the overall elimination rate of codeine. (codeine Vd is 2.6 L/kg, half life = 3 hr, morphine Vd is 3.3 L/kg, and half life is 2 hr)
Codeine plasma conc-time profile is
not different in the two populations
since lower CYP2D6 does not affect
the overall disposition rate of codeine.
Morphine plasma concentration is
lower in patients with lower CYP2D6
level because smaller fraction of
codeine dose is converted to morphine.
Answer
Morphine to codeine concentration ratio:
a-In patients with normal CYP2D6
b-In patients with abnormal CYP2D6
