Chapter 3: Pharmacokinetics
Mr Jones has zero kidney function and is undergoing hemodialysis while awaiting a kidney transplant. He takes metformin for type 2 diabetes mellitus and was previously stabilized (while his kidney function was adequate) at a dosage of 500 mg twice daily, given orally. The plasma concentration at this dosage with normal kidney function was found to be 1.4 mg/L. He has been on dialysis for 10 days and metformin toxicity is suspected. A blood sample now shows a metformin concentration of 4.2 mg/L. What was Mr. Jones’ clearance of metformin while his kidney function was normal?
Examination questions often provide more information than is needed—to test the student’s ability to classify and organize data. In question 1, the data provided for Mr Jones on dialysis is irrelevant, even though choice A, 238 L/d, is the correct clearance while on dialysis. By definition, clearance is calculated by dividing the rate of elimination by the plasma concentration:
Ms Smith, a 65-year-old woman with pneumonia, was given tobramycin, 150 mg, intravenously. After 20 minutes, the plasma concentration was measured and was found to be 3 mg/L. Assuming no elimination of the drug in 20 minutes, what is the apparent volume of distribution of tobramycin in Ms Smith?
The volume of distribution (Vd) is the apparent volume into which the loading dose is distributed. It is calculated by dividing the dose by the resulting plasma concentration, Cp:
St John’s Wort, a popular botanical remedy, is a potent inducer of hepatic phase I CYP3A4 enzymes. Verapamil and phenytoin are both eliminated from the body by metabolism in the liver. Verapamil has a clearance of 1.5 L/min, approximately equal to liver blood flow, whereas phenytoin has a clearance of 0.1 L/min. Based on this fact, which of the following is most correct?
(A) St John’s Wort will increase the half-life of phenytoin and verapamil
(B) St John’s Wort will decrease the volume of distribution of CYP3A4 substrates