Related Experiment Video
Updated: Jul 10, 2026

High-throughput Identification of Synergistic Drug Combinations by the Overlap2 Method
Published on: May 21, 2018
Elevated gatifloxacin and reduced rifampicin concentrations in a single-dose interaction study amongst healthy
Helen McIlleron1, Jennifer Norman, Thomas P Kanyok
1Division of Clinical Pharmacology, Department of Medicine, Groote Schuur Hospital, University of Cape Town, South Africa. helen.mcilleron@uct.ac.za
Objectives:
Pharmacokinetic drug-drug interactions were investigated between the fluoroquinolone gatifloxacin and a fixed dose combination (FDC) of rifampicin, isoniazid and pyrazinamide.
Patients And Methods:
The single-dose pharmacokinetics of the four drugs was evaluated in an open-label three-way cross-over study amongst 22 healthy volunteers following administration of gatifloxacin, the FDC or the two products together.
Results:
Modest but potentially important drug-drug interactions affecting gatifloxacin and rifampicin concentrations were detected. The elimination rate of gatifloxacin was reduced such that the AUC from 0 h to infinity was increased with a geometric mean ratio (GMR) [90% confidence interval (CI)] of 1.14 (1.10, 1.18). Conversely, the AUC from 0 h to infinity for rifampicin was reduced (GMR: 0.81, 90% CI: 0.81, 0.96) when rifampicin, isoniazid and pyrazinamide were given together with gatifloxacin.
Conclusions:
Studies in patients including pharmacokinetic evaluation at steady state, efficacy and toxicity are required to determine the importance of the interactions for use of the combination of gatifloxacin, rifampicin, isoniazid and pyrazinamide in the treatment of tuberculosis.
Related Concept Videos
Pharmacokinetics: Drug–Drug Interactions
Pharmacokinetics: Drug–Food and Drug–Viral Interactions
Inhibitors of Bacterial DNA Synthesis
Determination of Multiple Dosing Parameters: Steady-State, Minimum and Maximum Concentrations
Effect of Hepatic Disease on Pharmacokinetics: Dose Adjustments Due to Hepatic Impairment
Combined Effects of Drugs: Synergism
Such synergistic combinations...