absorbed (see section 2.6), not the dose administered. The relationship (8.12)
may also be used to calculate the clearance that occurs in a specific time by
simply measuring the AUC for that time.
Clearance will vary with body weight and so for comparison purposes values
are normally quoted per kilogram of body weight (Table 8.2). It also varies with
the degree of protein binding. A large proportion of a drug with a high degree of
protein binding will exhibit a lower clearance value, since it will not be so readily
available for elimination as a drug with a lower degree of protein binding.
Table 8.2 Clearance values of some drugsDrug Clearance (cm^3 min^1 kg^1 ) Drug Clearance (cm^3 min^1 kg^1 )
Atropine 8 Bumetamide 3
Bupivacaine 8 Caffeine 1–2
Disopyramide 0.5–2 (dose dependent) Ethambutol 9
Mepivacaine 5 Pentobarbitone 0.3–0.5
Ranitidine about 10 Vancomycin about 1
All drugs are carried to their site of action by the blood. The route normally
requires the drug to pass through several organs, where some of the drug may be
lost by elimination. This loss is known asextraction. The proportion of the drug
removed by a single transit of the total dose of the drug through the organ is
defined as:
E¼
CinCout
Cin
(8:13)
whereEis known as the extraction ratio. The extraction ratio has no units. Its
values range from zero to unity. A value of 0.4 means that 40 per cent of the
drug is irreversibly removed as it passes through the organ. The clearance of the
organ is related to the rate of blood flow by the relationship:
Cl¼QE (8:14)
whereQ(volume per unit time) is the rate of blood flow. Since the liver is a
major site of metabolism and excretion, the hepatic extraction values (EH)of
many drugs have been determined (Table 8.3). Leads whereEH~1 will seldom
reach the general circulatory system in sufficient quantity to be therapeutically
effective.
Clearance is a more useful concept in pharmacokinetics than eithert1/2orkel.
It enables blood flow rate, which controls the rate at which a drug is delivered to
168 PHARMACOKINETICS