required pharacological result. However, it should be realized that the final
decision as to which analogue to develop would not be based solely on its
bioavailabity. It would be based on a consideration of all the pharmacokinetic
and pharmacodynamic data obtained for the three analogues.
8.5.1 Single oral dose
When a single dose of a drug is administered orally its plasma concentration
increases to a maximum value (Cmax)attmaxbefore falling with time (Figure
8.9). The increase in plasma concentration occurs as the drug is absorbed. It is
accompanied by elimination, which starts from the instant the drug is absorbed.
The rate of elimination increases as the concentration of the drug in the plasma
increases to the maximum absorbed dose. At this point, the rate of absorption is
equal to the rate of elimination. Once absorption ceases, elimination becomes
the dominant pharmacokinetic factor and plasma concentration falls.
The change in plasma concentration–time curve for a single oral dose shows
the time (tlag) taken for the drug to reach its therapeutic window concen-
tration, the time (tmax) taken to reach the maximum plasma concentration
(Cmax) and the period of time (tdi) for which the plasma concentration lies within
the therapeutic window (Figure 8.9). However, in view of the difficulty of taking
serum samples at exactly the right time both tmax andCmax are normally
determined by calculation (see section 8.5.2). All these measurements are useful
in determining the correct dosage form for a drug and also the selection of
analogues for development.
ACpTimet...................................................................
............................
tlagCmax .......................
............................
tmax...................................................................
............................
}
Therapeutic
windowtdiFigure 8.9 The change in plasma concentration of a drug with time due to a single oral dose of
the drug. A small time lapse A occurs before the drug reaches the blood. This is mainly the time
taken for the drug to reach its site of absorption from the mouth
The absorption of a drug into the general circulatory system is a complex
process. Drugs given orally dissolve in the GI tract fluids before being absorbed
through the GI tract membrane. The rate of absorption depends on both the
174 PHARMACOKINETICS