In this episode, I’ll discuss the final 4 questions of a recent survey of intensive care professionals about clinically relevant pharmacokinetic knowledge on antibiotic dosing. This is part 3 of a 3 part series that began with episode 414.
The survey was published in May 2019 in the journal Critical Care and titled:
Lead author: Lucas M. Fleuren
Questions 9, 10, 11 and 12 all tie back into understanding the drivers behind drug half-life and how they can change in critical illness.
Question 9 lists volume of distribution and clearance and asks: “How do these parameters change in the initial phase of septic shock following adequate volume resuscitation?”
Both the volume of distribution and clearance increase in septic shock following adequate resuscitation. Volume of distribution increases because the added fluids add to the compartment that medications distribute into. Clearance increases because resuscitation restores adequate stroke volume and blood flow to vital organs such as the liver and kidney.
Questions 10 and 11 address the knowledge of the formula for calculating half-life, which is t1/2 = 0.693 × VD/CL.
Question 10 asks: “The volume of distribution of an antibiotic is 100 L. Clearance is 10 L/h. What is the half-life?” With knowledge of the half-life formula, we can calculate the half-life given these parameters for Vd and CL is 6.93 hours.
While this is not a calculation you should expect to make routinely, knowledge of this formula helps determine what happens to drug half-life when the parameters of the formula change. That is the subject of question 11 which asks:
“What happens to half-life if …
…volume of distribution increases?
…volume of distribution decreases?”
Because clearance is in the denominator of the half-life formula, it has an inverse relationship to half-life. That is to say as clearance increases, half-life falls and as clearance decreases, half-life increases.
Because volume of distribution is in the numerator of the half-life formula, it has a direct relationship to half-life. That is to say as volume of distribution increases, half-life increases and as volume of distribution falls, half-life falls.
With this information, the intensive care clinician can make logical predictions about the behaviors of an antibiotic in response to critical illness based on how the pathophysiology of the disease affects the pharmacokinetics of the antibiotic. It is this type of application of knowledge that is essential to personalize patient care when a situation which has not been addressed in a randomized controlled trial presents itself.
The final question relates to knowledge of how half-life affects the attainment of steady-state drug levels. Question 12 asks: “The half-life of an antibiotic is 3 h. When is steady state reached approximately following start of continuous infusion?”
Five half-lives is generally accepted as the point at which steady-state concentrations are achieved. This is because the concentration should be ~97% of steady-state after 5 half-lives.
This information is clinically relevant because it gives clinicians an idea of when a treatment they have started will reach its optimal effect. Combine this with knowledge of how pathophysiology in critical illness affects volume of distribution and clearance, and the clinician is prepared to make patient-specific adjustments to antibiotic therapy to ensure the best chance at a clinical cure.
Correlating parameters of a medication such as pharmacokinetics or mechanism of action with the pathophysiology of a disease is an essential step in applying your knowledge to the benefit of patients at the bedside. Members of my Hospital Pharmacy Academy have access to my Clinical Pharmacist Mindset training that offers practical advice on correlating medication parameters to pathophysiology of disease, as well as how to achieve and maintain credibility with the healthcare team, prioritize your workday, communicate with physicians, and build relationships with physicians and other medical professionals. This is just one of the over 80 training modules available 24/7 to Academy members as well as many other resources to help in your practice as a hospital pharmacist. To get immediate access to everything the Academy has to offer go to pharmacyjoe.com/academy to join today.
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