The following plasma concentration-time data were obtained after single iv bolus (66 mg) and oral (340 mg) doses of kinetolol.

Time (hr) 2 8 14 21 34

IV Conc. (mg/L) 3.02 1.77 1.01 0.559 0.169

Time (hr) 0.2 1 3 13 19 36

PO Conc. (mg/L) 1.45 5.64 9.42 4.12 2.25 0.515

I. Please estimate the following kinetic parameters from the iv data.

1. Plasma half life (t1/2 in hr)

2. Elimination rate constant (K in hr-1)

3. Volume of distribution (V in L)

4. AUC from zero to infinity (AUC in mg.hr/L)

5. Clearance using the AUC method (Cl in mL/min) II. Please estimate the following kinetic parameters from the po data.

6. Maximum plasma concentration (Cmax in mg/L)

7. Time to reach Cmax (tmax in hr)

8. Terminal plasma half life (t1/2-term in hr)

9. The terminal half life after PO dosing is related to the 1. Absorption process. 2. Elimination process.

10. Oral AUC (AUCPO in mg.hr/L)

11. Extent of oral bioavailability (F)

12. Clearance (Cl in mL/min)

13. Volume of distribution (V in L)

III. Please use the information obtained above to answer the following questions.

14. If the IV data were not available, which kinetic parameter could be estimated with certainty from the above PO data?

1. Absorption half life

2. Extent of oral Bioavailability

3. Elimination rate constant

4. Cmax 15.

Comparing the IV and PO data, which of the following answers is correct?

1. If the PO and IV doses are the same, the AUCs after PO and IV must be the same.

2. The volume of distribution values after PO and IV doses are expected to be different.

3. The terminal half life values after IV and PO administration of all drugs should always be similar.

4. In first-order kinetics, clearance and volume of distribution values are route independent (similar values after PO and IV administration).