Communicable is launching a new series on everything related to pharmacokinetics (PK) and pharmacodynamics (PD). Kicking off this series are hosts Thomas Tängdén, Erin McCreary and Angela Huttner, and invited guests Amy Legg and Rekha Pai Mangalore. They walk us through key parameters and terms of PK/PD, such as volume of distribution, minimum inhibitory concentration (MIC), epidemiological cut-off value (ECOFF), and PK/PD indices, laying the foundation to better comprehend clinical applications such as setting a clinical breakpoint and how it guides therapeutic drug monitoring (TDM). This first episode encompasses a broad scope across PK/PD theory, preparing the listener for subsequent episodes that will explore these topics with greater depth and make you love PK/PD. 

This episode was peer-reviewed by Ummu Afeera Zainulabid of the International Islamic University, Kuantan, Malaysia.   

Terms and definitions 

• ADME, a drug’s journey through the body: absorption, distribution, metabolism, excretion
• Volume of distribution, a parameter describing the theoretical volume that would be necessary to contain the total amount of an administered drug at the same concentration that it is observed in the blood plasma
• Clearance, the volume of blood cleared of drug per unit time
• Half-life, the time required for the concentration of a drug to decrease to half of its initial amount in the body
• Loading dose, a larger initial dose designed to rapidly bring drug levels into the therapeutic range
• Steady state, an equilibrial condition in which the rate of input of a drug is equal to the rate of its output
• MIC, minimum inhibitory concentration
• ECOFF, epidemiological cut-off value: the highest MIC value of isolates that are not known to have resistance and are therefore considered representative of wild-type bacterial isolates
• Clinical breakpoint setting, takes into account drug dosing, PK/PD, site of infection, clinical data; what we think is the breakpoint for the lab to call a bacterial organism susceptible to a drug
• PK/PD index, a parameter that describes the observed antimicrobial activity of an antimicrobial; there are three different indices: 
  1. T>MIC (bacterial killing depends on the drug concentration’s remaining higher than the MIC over time)
  2. Cmax/MIC (bacterial killing depends on the drug’s peak concentration)
  3. AUC/MIC (bacterial killing depends on the area under the curve over the MIC)
• TDM, therapeutic drug monitoring

Further reading

• Mouton JW, et al. MIC-based dose adjustment: facts and fables. J Antimicrob Chemother 2018. doi:10.1093/jac/dkx427
• Märtson A, et al. The pharmacokinetics of antibiotics in patients with obesity: a systematic review and consensus guidelines for dose adjustments. Lancet Infect Dis 2025. doi: 10.1016/S1473-3099(25)00155-0
• Eagle H and Musselman AD. The rate of bactericidal action of penicillin in vitro as a function of its concentration, and its paradoxically reduced activity at high concentrations against certain organisms. J Exp Med 1948. doi: 10.1084/jem.88.1.99