title: Factors influencing lopinavir and atazanavir plasma concentration.
abstract: BACKGROUND
  The protease inhibitors lopinavir and atazanavir are both recommended for treatment of HIV-infected patients. Considerable inter-individual variability in plasma concentration has been observed for both drugs. The aim of this study was to evaluate which demographic factors and concomitant drugs are associated with lopinavir and atazanavir plasma concentration.
  
  
  METHODS
  Data from the Liverpool TDM (therapeutic drug monitoring) Registry were linked with the UK Collaborative HIV Cohort (CHIC) study. For each patient, the first measurement of lopinavir (twice daily) or atazanavir [once daily, ritonavir boosted (/r) or unboosted] plasma concentration was included. Linear regression was used to evaluate the association of dose, gender, age, weight, ethnicity and concomitant antiretroviral drugs or rifabutin with log-transformed drug concentration, adjusted for time since last intake.
  
  
  RESULTS
  Data from 439 patients on lopinavir (69% 400 mg/r, 31% 533 mg/r; 3% concomitant rifabutin) and 313 on atazanavir (60% 300 mg/r, 32% 400 mg/r, 8% 400 mg) were included. Multivariable models revealed the following predictors for lopinavir concentration: weight (11% decrease per additional 10 kg; P = 0.001); dose (25% increase for 533 mg/r; P = 0.024); and rifabutin (116% increase; P < 0.001). For atazanavir the predictors were dose (compared with 300 mg/r: 40% increase for 400 mg/r, 67% decrease for 400 mg; overall P < 0.001) and efavirenz (32% decrease; P = 0.016) but not tenofovir (P = 0.54).
  
  
  CONCLUSIONS
  This analysis confirms that efavirenz decreases atazanavir concentrations, and there was a negative association of weight and lopinavir concentrations. The strong impact of rifabutin on lopinavir concentration should be studied further.
authors.affiliation: MRC Clinical Trials Unit, London, UK. ws@ctu.mrc.ac.uk
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Stöhr
authors.forename: David
authors.initials: D
authors.lastname: Back
authors.forename: David
authors.initials: D
authors.lastname: Dunn
authors.forename: Caroline
authors.initials: C
authors.lastname: Sabin
authors.forename: Alan
authors.initials: A
authors.lastname: Winston
authors.forename: Richard
authors.initials: R
authors.lastname: Gilson
authors.forename: Deenan
authors.initials: D
authors.lastname: Pillay
authors.forename: Teresa
authors.initials: T
authors.lastname: Hill
authors.forename: Jonathan
authors.initials: J
authors.lastname: Ainsworth
authors.forename: Brian
authors.initials: B
authors.lastname: Gazzard
authors.forename: Clifford
authors.initials: C
authors.lastname: Leen
authors.forename: Loveleen
authors.initials: L
authors.lastname: Bansi
authors.forename: Martin
authors.initials: M
authors.lastname: Fisher
authors.forename: Chloe
authors.initials: C
authors.lastname: Orkin
authors.forename: Jane
authors.initials: J
authors.lastname: Anderson
authors.forename: Margaret
authors.initials: M
authors.lastname: Johnson
authors.forename: Philippa
authors.initials: P
authors.lastname: Easterbrook
authors.forename: Sara
authors.initials: S
authors.lastname: Gibbons
authors.forename: Saye
authors.initials: S
authors.lastname: Khoo
mesh_terms: D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000097:blood* / Q000493:pharmacokinetics*; D000069446:Atazanavir Sulfate; D048588:Benzoxazines / Q000097:blood / Q000493:pharmacokinetics; D001835:Body Weight; D003521:Cyclopropanes; D005260:Female; D015658:HIV Infections / Q000188:drug therapy; D006801:Humans; D061466:Lopinavir; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000097:blood* / Q000493:pharmacokinetics*; D010949:Plasma / Q000737:chemistry*; D011725:Pyridines / Q000097:blood* / Q000493:pharmacokinetics*; D011744:Pyrimidinones / Q000097:blood* / Q000493:pharmacokinetics*; D017828:Rifabutin / Q000097:blood / Q000493:pharmacokinetics; D006113:United Kingdom
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D009842:Oligopeptides; D011725:Pyridines; D011744:Pyrimidinones; D017828:Rifabutin; D061466:Lopinavir; D000069446:Atazanavir Sulfate; C098320:efavirenz