Metabolite Elimination

The metabolite concentration-time profile depends on the metabolite formation rate and elimination rate. The metabolite concentration during the elimination phase declines at a rate equal to the slower of the metabolite elimination rate and the metabolite formation rate.

a- When k(m) < k

i.e. the metabolite half life is longer than the parent drug half life.

The metabolite concentration declines at a rate dependent on the metabolite elimination rate constant k(m).

The decline in the metabolite conc is
limited by its elimination rate.
( elimination rate limited metabolite)

Remember that the the elimination rate constant and the half life for the parent drug and for the metabolite are dependent on the total body clearance and Vd for the parent drug and the metabolite:

k =

CLT

Vd =

0.693

t1/2
k(m) =

CLT(m)

Vd(m) =

0.693

t1/2(m)

Mathematically:

Cp(m) =

k D

Vd(m)( k(m) -k) (e-k t - e-k(m) t)

The term e-k t approaches zero faster than the term e-k (m) t (because k(m) < k)

As time gets bigger, the equation is reduced to:

Cp(m) =

k D

Vd(m)( k(m) -k) ( e-k(m) t)
  • Page 1 of 2
  • 1
  • 2