Skip to Main Content

Content Update

October 1, 2019

Vancomycin Area Under the Concentration-Time Curve Threshold Associated with Nephrotoxicity: Vancomycin remains a mainstay of treatment for methicillin-resistant Staphylococcus aureus (MRSA) infection. Because of the high mortality rate associated with MRSA infections, clinicians target higher vancomycin trough concentrations (15-20 mg/L) to attain the optimal efficacy target of area under the curve to minimum inhibitory concentration ratio (AUC/MIC) ≥ 400. However, a vancomycin trough concentration >15 mg/L increases the risk of nephrotoxicity. AUC has been identified as a better predictor of vancomycin-induced nephrotoxicity. Recent studies analyzed the relationship between vancomycin AUCs and risk of nephrotoxicity using the Bayesian method. An AUC <650 mg*h/L is suggested as an acceptable threshold of vancomycin nephrotoxicity in both adults and pediatric patients. Proposed vancomycin dosing guidelines recommend AUC/MIC of 400-600 assuming a vancomycin MIC of ≤1 mg/L as new pharmacokinetic-pharmacodynamic (PK/PD) target for maximal efficacy and minimal nephrotoxicity in patients with MRSA infections. AUC-guided vancomycin dosing may need the utilization of Bayesian software programs.

KEY CONCEPTS

KEY CONCEPTS

  • image Clinical pharmacokinetics is the discipline that describes the absorption, distribution, metabolism, and elimination of drugs in patients requiring drug therapy.

  • image Clearance is the most important pharmacokinetic parameter because it determines the steady-state concentration for a given dosage rate. Physiologically, clearance is determined by blood flow to the organ that metabolizes or eliminates the drug and the efficiency of the organ in extracting the drug from the bloodstream.

  • image The volume of distribution is a proportionality constant that relates the amount of drug in the body to the serum concentration. The volume of distribution is used to calculate the loading dose of a drug that will immediately achieve a desired steady-state concentration. The value of the volume of distribution is determined by the physiologic volume of blood and tissues and how the drug binds in blood and tissues.

  • image Half-life is the time required for serum concentrations to decrease by one-half after absorption and distribution are complete. It is important because it determines the time required to reach steady state and the dosage interval. Half-life is a dependent kinetic variable because its value depends on the values of clearance and volume of distribution.

  • image The fraction of drug absorbed into the systemic circulation after extravascular administration is defined as its bioavailability.

  • image Most drugs follow linear pharmacokinetics, whereby steady-state serum drug concentrations change proportionally with long-term daily dosing.

  • image Some drugs do not follow the rules of linear pharmacokinetics. Instead of steady-state drug concentration changing proportionally with the dose, serum concentration changes more or less than expected. These drugs follow nonlinear pharmacokinetics.

  • image Pharmacokinetic models are useful to describe data sets, to predict serum concentrations after several doses or different routes of administration, and to calculate pharmacokinetic constants such as clearance, volume of distribution, and half-life. The simplest case uses a single compartment to represent the entire body.

  • image Factors to be taken into consideration when deciding on the best drug dose for a patient include age, gender, weight, ethnic background, other concurrent disease states, and other drug therapy.

  • image Cytochrome P450 is a generic name for the group of enzymes that are responsible for most drug metabolism oxidation reactions. Several P450 isozymes have been identified, including CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4.

  • image Membrane transporters are protein molecules concerned with the active transport of drugs across cell membranes. ...

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.