What pharmacokinetic parameter of Rifampicin utilizes peak concentration rather than the AUC/MIC ratio?

From the Guidelines

Rifampicin's peak concentration is the pharmacokinetic parameter that utilizes peak concentration rather than the AUC/MIC ratio.

Pharmacokinetic Parameters

• The peak concentration of Rifampicin is a critical parameter in determining its efficacy, particularly for its bactericidal activity against M. tuberculosis 1.
• The AUC/MIC ratio is a key parameter for many antibiotics, but for Rifampicin, the peak concentration is more relevant due to its concentration-dependent killing mechanism.
• Rifampicin's peak serum concentrations of 7–14 mg/ml occur 1.5–3.0 h after ingestion, and it is quickly absorbed from the gastrointestinal tract 1.

Concentration-Dependent Killing

• Rifampicin exhibits concentration-dependent killing, where its bactericidal activity increases with increasing concentrations above the MIC of the pathogen 1.
• The peak:MIC ratio is an important parameter for antibiotics with concentration-dependent killing, such as Rifampicin, and a ratio of >10 is often associated with improved efficacy 1.

Clinical Implications

• The use of Rifampicin's peak concentration as a pharmacokinetic parameter has important implications for its dosing and administration in clinical practice, particularly in the treatment of tuberculosis 1.

From the FDA Drug Label

After intravenous administration of a 300 or 600 mg dose of rifampin infused over 30 minutes to healthy male volunteers (n=12), mean peak plasma concentrations were 9.0 ± 3.0 and 17.5 ± 5.0 mcg/mL, respectively. The pharmacokinetic parameter of Rifampicin that utilizes peak concentration rather than the AUC/MIC ratio is the minimum inhibitory concentration (MIC) for certain types of infections, but the provided text does not explicitly state this. However, it can be inferred that peak concentration is relevant for rifampin, as the text provides information on peak plasma concentrations after administration of different doses. 2

• The peak concentration is an important parameter for rifampin, as it is used to determine the effectiveness of the drug against certain microorganisms.
• The provided text does not explicitly state which pharmacokinetic parameter utilizes peak concentration, but it provides information on the peak plasma concentrations of rifampin after administration of different doses.

From the Research

Pharmacokinetic Parameter of Rifampicin

• The pharmacokinetic parameter of Rifampicin that utilizes peak concentration rather than the AUC/MIC ratio is the maximum (peak) concentration (Cmax) 3.
• A Rifampicin Cmax > 8.2 μg/mL is an independent predictor of sterilizing activity, and therapeutic drug monitoring at 2,4, and 6 h post-dose may aid in optimizing dosing to achieve the recommended rifampicin concentration of ≥ 8 µg/mL 3.
• For severe forms of TB, such as TB meningitis, a higher rifampicin Cmax is required, with Cmax ≥ 22 μg/mL associated with reduced mortality 3.
• The Cmax/MIC ratio is also considered a predictive pharmacokinetic-pharmacodynamic parameter for determinations of efficacy, in addition to the AUC/MIC ratio 4, 3.