title: Effect of intermittent rifampicin on the pharmacokinetics and safety of raltegravir.
abstract: OBJECTIVE
  Previous studies of raltegravir and rifampicin have not studied the interaction when rifampicin is dosed intermittently. This study aimed to assess the pharmacokinetics of twice daily raltegravir and intermittently dosed rifampicin.
  
  
  METHODS
  This was a prospective, open, single-arm, three-part, controlled study in healthy volunteers. Over a period of 38 days subjects received 5 days of standard-dose raltegravir (400 mg twice daily) followed by 28 days of standard-dose raltegravir plus rifampicin three times a week followed by 5 days of high-dose (800 mg twice daily) raltegravir plus rifampicin three times a week. Pharmacokinetic sampling was performed on days 5, 33 and 38. Raltegravir pharmacokinetic parameters were determined by non-compartmental analysis and reported as geometric means and 90% CIs. ClinicalTrials.gov: NCT01424826.
  
  
  RESULTS
  Sixteen subjects (12 females) completed the study. Raltegravir trough plasma concentration (C12) was significantly lower in the presence of rifampicin when dosed at 400 mg twice daily (40%), which was not observed with 800 mg twice daily dosing. Raltegravir Cmax and AUC0-12 were both significantly higher in the presence of rifampicin when dosed at 800 mg twice daily (76% and 84%, respectively), but this dose was well tolerated.
  
  
  CONCLUSIONS
  This study suggests that rifampicin induction of raltegravir is comparable between daily and intermittent rifampicin. In the absence of definitive clinical efficacy data to suggest otherwise, doses of 800 mg of raltegravir twice daily with rifampicin thrice weekly are well tolerated and yield higher AUCs and comparable C12 when compared with raltegravir alone.
authors.affiliation: Royal Liverpool & Broadgreen University Hospitals NHS Trust, Prescot Street, Liverpool, UK.
authors.forename: Helen E
authors.initials: HE
authors.lastname: Reynolds
authors.affiliation: Royal Liverpool & Broadgreen University Hospitals NHS Trust, Prescot Street, Liverpool, UK.
authors.forename: Ales
authors.initials: A
authors.lastname: Chrdle
authors.affiliation: Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
authors.forename: Deirdre
authors.initials: D
authors.lastname: Egan
authors.affiliation: Royal Liverpool & Broadgreen University Hospitals NHS Trust, Prescot Street, Liverpool, UK.
authors.forename: Mas
authors.initials: M
authors.lastname: Chaponda
authors.affiliation: Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
authors.forename: Laura
authors.initials: L
authors.lastname: Else
authors.affiliation: Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
authors.forename: Justin
authors.initials: J
authors.lastname: Chiong
authors.affiliation: Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Back
authors.affiliation: Royal Liverpool & Broadgreen University Hospitals NHS Trust, Prescot Street, Liverpool, UK Institute of Translational Medicine, University of Liverpool, Liverpool, UK khoo@liv.ac.uk.
authors.forename: Saye H
authors.initials: SH
authors.lastname: Khoo
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D000904:Antibiotics, Antitubercular / Q000008:administration & dosage*; D060085:Coinfection / Q000188:drug therapy; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005260:Female; D015658:HIV Infections / Q000188:drug therapy; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008875:Middle Aged; D011760:Pyrrolidinones / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D000068898:Raltegravir Potassium; D012293:Rifampin / Q000008:administration & dosage*; D014376:Tuberculosis / Q000188:drug therapy; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D000904:Antibiotics, Antitubercular; D011760:Pyrrolidinones; D000068898:Raltegravir Potassium; D012293:Rifampin
keywords: HIV; PK; TB