title: Pharmacokinetics of plasma lopinavir/ritonavir following the administration of 400/100 mg, 200/150 mg and 200/50 mg twice daily in HIV-negative volunteers.
abstract: OBJECTIVE
  Data suggest that some licensed antiretroviral doses could be reduced. We assessed the safety, tolerability and pharmacokinetics of lopinavir/ritonavir at doses of 400/100, 200/150 and 200/50 mg twice daily in HIV-negative volunteers (http://clinicaltrials.gov/ct2/show/NCT00985543).
  
  
  METHODS
  Male and female volunteers were administered lopinavir/ritonavir at doses of 400/100 mg (two lopinavir/ritonavir Meltrex 200/50 mg tablets, Regimen 1), 200/150 mg (one Meltrex tablet, one 100 mg ritonavir capsule, Regimen 2) and 200/50 mg (one Meltrex tablet, Regimen 3). Each dose was given twice daily for 7 days sequentially, separated by a 7 day wash-out period. Lopinavir/ritonavir steady-state pharmacokinetics was assessed over 12 h at the end of each phase (days 7, 21 and 35). Pharmacokinetic parameters were compared using the 400/100 mg twice daily dose as reference, by determining geometric mean ratios (GMRs) and 90% confidence intervals.
  
  
  RESULTS
  Twenty-two subjects (eight females) completed the study. Lopinavir AUC(0-12) (ng h/mL), C(max) (ng/mL) and the minimum concentration (C(trough)) (ng/mL) for the 400/100, 200/150 and 200/50 mg twice daily doses, respectively, were as follows: 99,599, 73,603 and 45,146; 11,965, 8939 and 6404; and 5776, 4293 and 1749. Lopinavir pharmacokinetic parameters were significantly lower for Regimens 2 and 3: GMR (90% CI) AUC(0-12), 0.74 (0.65-0.84) and 0.45 (0.40-0.51); C(max), 0.75 (0.66-0.85) and 0.54 (0.40-0.60); and C(trough), 0.74 (0.62-0.89) and 0.30 (0.25-0.36), respectively. All subjects taking the 400/100 and 200/150 mg twice daily doses, and 19 (86%) subjects taking 200/50 mg twice daily had lopinavir concentrations above the suggested minimum effective concentration of 1000 ng/mL.
  
  
  CONCLUSIONS
  These pharmacokinetic data show that therapeutic plasma concentrations of lopinavir can be achieved with 200/150 mg of lopinavir/ritonavir twice daily (one Meltrex tablet and one 100 mg ritonavir capsule twice daily).
authors.affiliation: St Stephen's Centre, Chelsea and Westminster Hospital, London, UK. akil.jackson@chelwest.nhs.uk
authors.forename: Akil
authors.initials: A
authors.lastname: Jackson
authors.forename: Andrew
authors.initials: A
authors.lastname: Hill
authors.forename: Rebekah
authors.initials: R
authors.lastname: Puls
authors.forename: Laura
authors.initials: L
authors.lastname: Else
authors.forename: Janaki
authors.initials: J
authors.lastname: Amin
authors.forename: David
authors.initials: D
authors.lastname: Back
authors.forename: Enmoore
authors.initials: E
authors.lastname: Lin
authors.forename: Saye
authors.initials: S
authors.lastname: Khoo
authors.forename: Sean
authors.initials: S
authors.lastname: Emery
authors.forename: Roland
authors.initials: R
authors.lastname: Morley
authors.forename: Brian
authors.initials: B
authors.lastname: Gazzard
authors.forename: Marta
authors.initials: M
authors.lastname: Boffito
mesh_terms: D000284:Administration, Oral; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D006805:Human Experimentation; D006801:Humans; D061466:Lopinavir; D008297:Male; D008875:Middle Aged; D010949:Plasma / Q000737:chemistry*; D011744:Pyrimidinones / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D019438:Ritonavir / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*
chemical_list: D019380:Anti-HIV Agents; D011744:Pyrimidinones; D061466:Lopinavir; D019438:Ritonavir