European Journal of Clinical Pharmacology

, Volume 60, Issue 2, pp 109–114 | Cite as

Rifampicin seems to act as both an inducer and an inhibitor of the metabolism of repaglinide

  • Tanja Busk BidstrupEmail author
  • Nicolaj Stilling
  • Per Damkier
  • Birgitte Scharling
  • Mikael Søndergård Thomsen
  • Kim Brøsen
Pharmacokinetics and Disposition



To investigate if rifampicin is both an inducer and an inhibitor of repaglinide metabolism, it was determined whether the timing of rifampicin co-administration influences the pharmacokinetics of repaglinide.


Male volunteers (n=12) participated in a randomised, two-period, crossover trial evaluating the effect of multiple doses of 600 mg rifampicin once daily for 7 days on repaglinide metabolism. Subjects were, after baseline measurements of repaglinide pharmacokinetics, randomised to receive, on either day 7 or day 8 of the rifampicin administration period, a single dose of 4 mg repaglinide and vice versa in the following period.


When repaglinide was given, together with the last rifampicin dose, on day 7, an almost 50% reduction of the median repaglinide area under the plasma concentration–time curve (AUC) was observed. Neither the peak plasma concentration (Cmax), time to reach Cmax (tmax) nor terminal half-life (t1/2) was statistically significantly affected. When repaglinide was given on day 8, 24 h after the last rifampicin dose, an almost 80% reduction of the median repaglinide AUC was observed. The median Cmax was now statistically significantly reduced from 35 ng/ml to 7.5 ng/ml. Neither tmax nor t1/2 was significantly affected.


When rifampicin and repaglinide are administered concomitantly, rifampicin seems to act as both an inducer and an inhibitor of the metabolism of repaglinide. After discontinuing rifampicin administration, while the inductive effect on CYP3A4 and probably also CYP2C8 is still present, an even more marked reduction in the plasma concentration of repaglinide was observed. Our results suggest that concomitant administration of rifampicin and repaglinide may cause a clinically relevant decrease in the glucose-lowering effect of repaglinide, in particular when rifampicin treatment is discontinued or if the drugs are not administered simultaneously or within a few hours of each other.


Repaglinide Rifampicin Interaction 



Novo Nordisk A/S, Denmark, financed this study. This experiment complies with the current law of the country in which it was performed (Denmark).


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Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Tanja Busk Bidstrup
    • 1
    Email author
  • Nicolaj Stilling
    • 1
  • Per Damkier
    • 2
  • Birgitte Scharling
    • 3
  • Mikael Søndergård Thomsen
    • 4
  • Kim Brøsen
    • 1
  1. 1.Clinical PharmacologyUniversity of Southern DenmarkOdense CDenmark
  2. 2.Dept. KKA, Clinical PharmacologyOdense University HospitalDenmark
  3. 3.Clinical PharmacologyNovo Nordisk A/SDenmark
  4. 4.Prosidion Ltd.OxfordUK

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