Pharmacokinetic Questions

Question 1: A patient requires an intravenous (IV) infusion of an active pharmaceutical ingredient (API) which obeys the one-compartment pharmacokinetic model. The therapeutic plasma concentration (Ç) for the API is 35 mg L’², the API’s volume of distribution (v) is 18.4 L and the API’s elimination constant (k_) is 0.165 hr2.

(a) Calculate a suitable infusion rate (in mghr² which will achieve the therapeutic plasma concentration when administered over 30min. (6 marks)

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(b) Calculate the infusion rate (in mg hr² which will maintain the therapeutic plasma concentration once steady state has been achieved by the loading infusion performedin (a) above. (6 marks)

(c) The maintenance infusion was terminated because the patient developed 20 % renal failure due to the illness. The plasma concentration upon stopping was found to be 35 mg L’ (i.e. ) Indicate how and why renal failure is likely to affect a patient’s plasma level of a drug substance. (2 marks)

(d) Therapeutic drug monitoring determined Cp 5 hr after stopping the infusion to be 15.72mg L’ Calculate kd and an appropriate infusion rate which would maintain the therapeutic plasma concentration (6 marks)

Question2: The drug cournarin is metabolised to aconjugate as shown below: OH SG – Metabolite A C

(a) Draw the structure of metabolite A and identify the type of conjugate produced (2 marks)

(b) Discuss the conjugation enzyme involved, highlighting its subcellular localisation, cofactor requirements and the biosynthetic pathway of the conjugate moiety (11 marks)

(c) The conjugate is further metabolised to a mercapturate as shown below: Draw the structures of metabolites B and C and discuss their formation and excretion. marks) OF .GG Metabolite B Metabolite C

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