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British journal of clinical pharmacology
05, 2017;83 (5): 1039-1047.

Population pharmacokinetics of rifampicin in adult patients with osteoarticular infections: interaction with fusidic acid.

Amélie Marsot, Amelie Ménard, Julien Dupouey, Cedric Muziotti, Romain Guilhaumou, Olivier Blin
Author Information
  1. Amélie Marsot: Service de Pharmacologie Clinique et Pharmacovigilance, Hôpital de la Timone, Marseille, 264 rue saint pierre, 13385, Marseille, France.
  2. Amelie Ménard: Pôle des Maladies Infectieuses et Tropicales Clinique et Biologique, Service de Maladies Infectieuses, Fondation IHU Méditerranée Infection, Centre Hospitalo-Universitaire Conception, 147, Boulevard Baille, 13385, Marseille cedex 05, France.
  3. Julien Dupouey: Service de Pharmacologie Clinique et Pharmacovigilance, Hôpital de la Timone, Marseille, 264 rue saint pierre, 13385, Marseille, France.
  4. Cedric Muziotti: Service de Pharmacologie Clinique et Pharmacovigilance, Hôpital de la Timone, Marseille, 264 rue saint pierre, 13385, Marseille, France.
  5. Romain Guilhaumou: Service de Pharmacologie Clinique et Pharmacovigilance, Hôpital de la Timone, Marseille, 264 rue saint pierre, 13385, Marseille, France.
  6. Olivier Blin: Service de Pharmacologie Clinique et Pharmacovigilance, Hôpital de la Timone, Marseille, 264 rue saint pierre, 13385, Marseille, France.
PMID: 27813241 DOI: 10.1111/bcp.13178

Abstract

AIMS: Rifampicin represents the key antibiotic for the management of osteoarticular infections. An important pharmacokinetic variability has already been described, particularly for absorption and metabolism. All previous pharmacokinetic studies have been focused only on patients treated for tuberculosis. The objective of the present study was to describe a population pharmacokinetic model of rifampicin in patients with staphylococcal osteoarticular infections, which has not been investigated to date.
METHOD: Rifampicin concentrations were collected retrospectively from 62 patients treated with oral rifampicin 300 mg three times daily. Plasma concentration-time data were analysed using NONMEM to estimate population pharmacokinetic parameters. Demographic data, infection characteristics and antibiotics taken in addition to rifampicin antibiotics were investigated as covariates.
RESULTS: A one-compartment model, coupled to a transit absorption model, best described the rifampicin data. Fusidic acid coadministration was identified as a covariate in rifampicin pharmacokinetic parameters. The apparent clearance and apparent central volume of distribution mean values [95% confidence interval (CI)] were 5.1 1 h (1.2, 8.2 1 h )/23.8 l (8.9, 38.7 l) and 13.7 1 h (10.6, 18.0 1 h )/61.1 1 (40.8, 129.0 1) for patients with and without administration of fusidic acid, respectively. Interindividual variability (95% CI) in the apparent clearance and apparent central volume of distribution were 72.9% (49.5, 86.0%) and 59.1% (5.5, 105.4%), respectively. Residual variability was 2.3 mg l (1.6, 2.6 mg l ).
CONCLUSION: We developed the first population pharmacokinetic model of rifampicin in patients with osteoarticular infections. Our model demonstrated that fusidic acid affects rifampicin pharmacokinetics, leading to potential high drug exposure. This finding suggests that fusidic acid dosing regimens should be reconsidered.

Keywords

NONMEM fusidic acid osteoarticular infections population pharmacokinetics rifampicin

References

  1. Klin Wochenschr. 1985 Dec 2;63(23):1205-11 [PMID: 4087830]
  2. N Engl J Med. 2004 Oct 14;351(16):1645-54 [PMID: 15483283]
  3. Antimicrob Agents Chemother. 2008 Jun;52(6):2138-48 [PMID: 18391026]
  4. J Clin Pharm Ther. 2013 Feb;38(1):56-61 [PMID: 23167603]
  5. Drugs. 2014 Jun;74(8):839-54 [PMID: 24846578]
  6. Drug Metab Rev. 1981;12(1):159-218 [PMID: 7028436]
  7. Clin Infect Dis. 2011 Aug;53(4):334-40 [PMID: 21810745]
  8. Antimicrob Agents Chemother. 2009 Sep;53(9):3880-6 [PMID: 19564363]
  9. Br J Clin Pharmacol. 2017 May;83(5):1039-1047 [PMID: 27813241]
  10. Br J Pharmacol. 2015 Dec;172(24):6024-109 [PMID: 26650445]
  11. Br J Clin Pharmacol. 2000 Jul;50(1):82-3 [PMID: 10886126]
  12. Can Respir J. 2011 Jul-Aug;18(4):225-9 [PMID: 22059181]
  13. J Antimicrob Chemother. 2004 Jun;53(6):928-35 [PMID: 15117932]
  14. Pulm Pharmacol Ther. 2012 Feb;25(1):83-6 [PMID: 22179055]
  15. Comput Methods Programs Biomed. 2008 May;90(2):154-66 [PMID: 18215437]
  16. Clin Infect Dis. 2013 Jan;56(1):1-10 [PMID: 23230301]
  17. Br J Pharmacol. 1971 Sep;43(1):151-60 [PMID: 5136455]
  18. J Antimicrob Chemother. 1997 Jun;39(6):803-9 [PMID: 9222051]
  19. J Pharm Pharmacol. 2014 Oct;66(10):1421-8 [PMID: 24841364]
  20. J Antibiot (Tokyo). 2007 Sep;60(9):572-6 [PMID: 17917240]
  21. J Antimicrob Chemother. 1990 Feb;25 Suppl B:23-31 [PMID: 2312443]
  22. J Antimicrob Chemother. 2015 Dec;70(12):3298-306 [PMID: 26342028]
  23. J Clin Pharmacol. 2016 May;56(5):622-7 [PMID: 26387492]
  24. Antimicrob Agents Chemother. 2015 Nov 09;60(1):487-94 [PMID: 26552972]
  25. Clin Drug Investig. 2003;23(7):463-72 [PMID: 17535057]
  26. Rev Med Interne. 2013 Jan;34(1):39-41 [PMID: 23102978]
  27. J R Coll Physicians Edinb. 2010 Mar;40(1):33-6 [PMID: 21125037]
  28. Antimicrob Agents Chemother. 2006 Jan;50(1):55-61 [PMID: 16377667]
  29. Med Mal Infect. 2009 Oct;39(10):745-74 [PMID: 19877362]
  30. Nucleic Acids Res. 2016 Jan 4;44(D1):D1054-68 [PMID: 26464438]
  31. J Pharmacokinet Pharmacodyn. 2007 Oct;34(5):711-26 [PMID: 17653836]
  32. J Pharm Pharmacol. 1981 Mar;33(3):179-82 [PMID: 6116764]
  33. Antimicrob Agents Chemother. 1993 Mar;37(3):501-6 [PMID: 8460918]
  34. Int J Clin Pharmacol Ther. 1999 Nov;37(11):562-6 [PMID: 10584978]
  35. Chemotherapy. 1971;16(6):356-70 [PMID: 5145008]

MeSH Term

Administration, Oral
Adult
Aged
Aged, 80 and over
Anti-Bacterial Agents
Bone Diseases, Infectious
Female
Fusidic Acid
Humans
Joint Diseases
Male
Middle Aged
Models, Biological
Nonlinear Dynamics
Retrospective Studies
Rifampin
Staphylococcal Infections
Young Adult

Chemicals

Anti-Bacterial Agents
Fusidic Acid
Rifampin
Journal Article
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Word Cloud

Created with Highcharts 10.0.0rifampicinpharmacokineticpatientsacidosteoarticularmodelfusidicinfectionspopulationapparent5hvariabilitydata28pharmacokineticsRifampicindescribedabsorptiontreatedinvestigatedNONMEMparametersantibioticsclearancecentralvolumedistributionCI1 1160 1respectivelylAIMS:representskeyantibioticmanagementimportantalreadyparticularlymetabolismpreviousstudiesfocusedtuberculosisobjectivepresentstudydescribestaphylococcaldateMETHOD:concentrationscollectedretrospectively62oral300 mgthreetimesdailyPlasmaconcentration-timeanalysedusingestimateDemographicinfectioncharacteristicstakenadditioncovariatesRESULTS:one-compartmentcoupledtransitbestFusidiccoadministrationidentifiedcovariatemeanvalues[95%confidenceinterval]2 1/238 l9387 l137 11018/6140129withoutadministrationInterindividual95%729%49860%591%1054%Residual3 mg6 mgCONCLUSION:developedfirstdemonstratedaffectsleadingpotentialhighdrugexposurefindingsuggestsdosingregimensreconsideredPopulationadultinfections:interaction

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