Pharmacokinetics/Pharmacodynamics

Patient Cases

R.H. is 20-year-old man who presents to the emergency department with nausea and vomiting. His vital

signs are significant for heart rate 130 beats/minute, blood pressure 98/62 mm Hg, and respiratory rate 28

breaths/minute. Laboratory tests reveal an arterial blood gas significant for a pH of 7.11, Pco2 of 18 mm

Hg, and bicarbonate of 5.2 mEq/L. His basic metabolic panel is significant for potassium concentration

5 mEq/L, BUN 22 mg/dL, SCr 1.4 mg/dL, and blood glucose 400 mg/dL. Which changes would be most

likely to occur in the Vd of a weak acid like ciprofloxacin in this patient?

B.B. is a 62-year-old woman admitted to the ICU for septic shock. She has received 6 L of crystalloids in

the past 24 hours, including her initial resuscitation and maintenance fluids. The Vd for which one of the

following antibiotics would most likely be unaffected by the amount of intravenous fluids administered?

the GI tract, kidneys, lung, and brain. The greatest extent of knowledge regarding drug metabolism and,

more importantly, changes in critically ill patients relates to hepatic metabolism. Therefore, this section

will focus largely on changes in the hepatic metabolism of drugs, specifically high and low extraction ratio

drugs. However, the next section briefly discusses renal metabolism because the clinical ramifications of

drug metabolism in the kidney are a potential area for future research.

Data suggest that CYP 2C8, 2C9, and 3A4 are also expressed in the kidneys. In addition, UGT (UDP-

glucuronosyltransferase) enzymes 1A9 and 2B7 are abundantly expressed in the kidneys and play a role

in the glucuronidation of drugs. However, no data describe how changes in critically ill patients affect

drug metabolism in the kidneys by these enzymes. As evidenced by increased hypoglycemic events and

lower insulin requirements in critically ill patients with AKI, clinically relevant changes in renal insulin

metabolism occur, but the exact mechanisms for these are not well characterized (Nutrition 2011;27:766-72).