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Journal of the International AIDS Society

Open Access

Pharmacokinetics of plasma lopinavir/ritonavir following the administration of 400/100, 200/150, and 200/50 mg twice daily in HIV-negative volunteers

  • AGA Jackson1,
  • A Hill2,
  • LJ Else3,
  • DJ Back3,
  • R Morley4,
  • R Puls5,
  • J Amin5,
  • E Lin5 and
  • M Boffito4
Journal of the International AIDS Society201013(Suppl 4):P180

Published: 8 November 2010


RitonavirCommon Adverse EffectFemale VolunteerPositive SubjectMinimum Effective Concentration

Purpose of the study

Development and post-marketing data suggest that some licensed ARV doses could be reduced. We assessed the pharmacokinetics (PK) of lopinavir/ritonavir (LPV/r) following the administration of 3 different doses to HIV negative volunteers as a preliminary to the design of clinical trials to examine the safety and efficacy of novel dose regimens in HIV positive subjects.


Following written consent, male and female volunteers were administered LPV/r 400/100 (2 LPV/r Meltrex 200/50 tablets; regimen 1), 200/150 (1 Meltrex tablet, 1 100mg ritonavir capsule; regimen 2), and 200/50 (1 Meltrex tablet; regimen 3) mg twice daily (BID) for 7 days sequentially. Each 7-day phase was separated by a 7-day wash-out period and LPV/r steady-state PK was assessed over 12 hours on the last day of each dosing phase (days 7, 21 and 35). PK parameters were compared using Phase 1 as reference by determining geometric mean ratios (GMR) and 90% confidence intervals (CI). Safety and tolerability were assessed throughout the study period.

Summary of results

Twenty-two subjects (8 female) were enrolled and completed the study. GM PK parameters (90% CI) of the 3 doses are shown in Table 1.

Table 1

PK parameter

400/100 BID

200/150 BID

200/50 BID


regimen 1

regimen 2

regimen 3



AUC0-12 (ng.h/mL)

99599 (87180-113787)

73603 (65121-83191)

45146 (39251-51927)

Cmax (ng/mL)

11965 (10400-13766)

8939 (8047-9930)

6404 (5648-7262)

C12h (ng/mL)

5776 (4884-6831)

4293 (3603-5115)

1749 (1419-2156)



AUC0-12 (ng.h/mL)

4664 (3808-5664)

10462 (8972-12200)

1625 (1390-1899)

LPV PK parameters in regimens 2 and 3 were lower: GMR (90%CI) AUC 0.74 (0.65-0.84) and 0.45 (0.40-0.51); Cmax 0.75 (0.66-0.85) and 0.54 (0.40-0.60); C12h 0.74 (0.62-0.89) and 0.30 (0.25-0.36). All subjects in regimens 1 and 2 had LPV concentrations above the suggested minimum effective concentration (MEC) of 1000ng/mL, 3 subjects receiving regimen 3 had lower concentrations. No serious adverse events were observed and as expected mild/moderate diarrhoea was the most common adverse effect.


These PK data indicate that therapeutically relevant plasma concentrations of LPV can be achieved with lower administered doses and support further exploration of these lower LPV doses in properly designed randomised clinical trials. Preservation of therapeutically relevant LPV doses requires administration of higher doses of ritonavir. A new dose of LPV/r could lower cost and improve access in developing countries.

Authors’ Affiliations

Chelsea & Westminster Hospital, SSAT, London, UK
University of Liverpool and Tibotec BVBA, Pharmacology Research Laboratories, Liverpool, UK
Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, UK
Chelsea & Westminster Hospital, London, United Kingdom
University of New South Wales, Sydney, Australia


© Jackson et al; licensee BioMed Central Ltd. 2010

This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.