URINE DATA

FARMAKOKINETIK SM VI
 Urinary Drug Excretion Data

• Urinary drug excretion data is an indirect

method for estimating bioavailability. The drug
must be excreted in significant quantities as
unchanged drug in the urine.
• In addition, timely urine samples must be
collected and the total amount of urinary drug
excretion must be obtained
 D ∞
u

• The cumulative amount of drug excreted in the

urine, D ∞ u, is related directly to the total
amount of drug absorbed. Experimentally,
urine samples are collected periodically after
administration of a drug product. Each urine
specimen is analyzed for free drug using a
specific assay
Corresponding plots
relating the plasma
level–time curve and the
cumulative urinary drug
excretion
 dD u/dt
• dD u/dt. The rate of drug excretion. Because most drugs are eliminated by
a first-order rate process, the rate of drug excretion is dependent on the
first-order elimination rate constant k and the concentration of drug in
the plasma C p. In , the maximum rate of drug excretion, (dD u/dt)max, is at
point B, whereas the minimum rate of drug excretion is at points A and C.
Thus, a graph comparing the rate of drug excretion with respect to time
should be similar in shape as the plasma level–time curve for that drug .
• t ∞. The total time for the drug to be excreted. In and , the slope of the
curve segment A–B is related to the rate of drug absorption, whereas
point C is related to the total time required after drug administration for
the drug to be absorbed and completely excreted t = ∞. The t ∞ is a useful
parameter in bioequivalence studies that compare several drug products,
as will be described later in this chapter.
 Calculation of K from Urinary Excretion Data

• The elimination rate constant k may be

calculated from urinary excretion data. In this
calculation the excretion rate of the drug is
assumed to be first order. The term k e is the
renal excretion rate constant, and D u is the
amount of drug excreted in the urine
An alternative method for the calculation of the elimination rate constant
k from urinary excretion data is the sigma-minus method, or the
amount of drug remaining to be excreted method