Fundamentals of Medicinal Chemistry

Intravenous dosage (a) P 1 Elimination kel Elimination Two compartment model One compartment model Elimination Absorption Absorp ...

ately start to fall because of elimination processes (Figure 8.4(a) ). However, the plasma concentration of a drug administered ...

and C¼C 0 ekelt (8:2) whereC 0 is the plasma concentration of the drug in the body at a timet¼ 0, that is, the concentration im ...

(a) Co Cp LogeCp Log 10 Co Time Time (b) Figure 8.5 Determination ofCoby extrapolation of the plots of (a) theCpagainsttcurve an ...

for natural logarithms: lnCp¼lnC 0 kelt (8:6) and for logarithms to base 10: log 10 Cp¼log 10 C 0  kelt 2 : 303 (8:7) Both the ...

elimination of a drug from a defined region of the body to the plasma concen- tration of that drug. For example, the total clear ...

absorbed (see section 2.6), not the dose administered. The relationship (8.12) may also be used to calculate the clearance that ...

Table 8.3 The hepatic extraction values of some drugs DrugEHvalue<0.3 (low) DrugEHvalue 0.3–0.7 DrugEHvalue>0.7 (high) Ant ...

plasma concentration will fall, usually in an exponential curve, because the biological situation is now the same as if a dose o ...

(Css) may be calculated using Equation (8.21). This equation, which is derived from Equation (8.16) is based on the asumption th ...

orally administered drugs. Most orally administered drugs are absorbed through the membranes of the GI tract. The rate of absorp ...

whereEHis the hepatic extraction ratio. Therefore, leads with high hepatic extraction values (EH~1) will seldom reach the genera ...

required pharacological result. However, it should be realized that the final decision as to which analogue to develop would not ...

drug’s chemical nature and the physical conditions at the site of absorption. However, most drugs exhibit approximately first or ...

wherek 0 is the zero rate constant for the absorption process. However, it should be realised that some drug absorption and elim ...

Cp }PlateauCpvalues x x xxx xx Timet Figure 8.11 The general changes in plasma concentration with time for repeated oral doses. ...

that the absorption, elimination, distribution, clearance, bioavailability,t1/2and Vdof all existing and new drugs must be defin ...

(continued) (ii) the apparent volume of distribution of the drug, (iii) the clearance of the drug. What fundamental assumption h ...

(continued) (7) parameter(s) and indicate the best analogue for further investigation if a drug with a reasonable duration of ac ...

9 Drug Metabolism 9.1 Introduction Drug metabolism or biotransformations are the chemical reactions that are responsible for the ...