Drug Metabolism in Drug Design and Development Basic Concepts and Practice

AUC0– 1 is obtained from the rat pharmacokinetic data, and the test article
specific activity is derived from analysis of the dose formulation administered
to the rats.
If a tissue does not have an elimination phase and AUC0– 1 can not be
calculated, AUC0–tis used for calculating organ exposure.
The radiation absorbed dose in milliRad (mRad) is calculated as follows:

Dose ExposureðmCi=hÞSfactorðmRad=mCi hÞ

whereS-factor for [^14 C] is calculated in the following equation using human
tissue mass (Snyder et al., 1975; ICRP Publication 2003):

0 :105 rad g=mCi h=ðmass of human tissue in gramsÞ1000 mRad=Rad

TABLE 18.A3 Effective dose equivalent based on tissue distribution data.

Dose to human organ or tissue

Organ or tissuea

Weighting

factor

Radiation

absorbed doseb

(mRad or mrem)

Weighted

dose (mrem)

Bone marrow 0.12
Large intestine 0.12
Liver 0.05
Lung 0.12
Skin 0.01
Stomach 0.12
Testis 0.20
Thyroid 0.05
Urinary bladder 0.05
Remaining fivec,d
0.06
0.06
0.06
0.06
0.06

Effective dose equivalent (overall whole-body exposure, mrem) e
NC Not calculated.
aDose = weighting factor (from radiation absorbed dose. Organs ICRP (1990) analyzed are
critical organs as defined by ICRP 60 (1990).
bCalculated for a 100-mCi dose of radiolabeld article in humans.
cDose = weighting factor (from ICRP (1979)) radiation absorbed dose. Organs analyzed are those
five organs (excluding those analyzed per ICRP 60 (1990)) with the highest radiation absorbed dose.
dThe five organs or tissues receiving the largest absorbed dose (from Table 18.A1).
eValue varies depending on the radioactive exposures presented in Table 18.A1.

CONCLUSIONS AND PATH FORWARD 601