Skip to main content
SpringerLink
Log in

Comparison of the Plasma Pharmacokinetics of Lamivudine During Twice and Once Daily Administration in Patients with HIV

  • Original Research Article
  • Published:
Clinical Pharmacokinetics Aims and scope Submit manuscript

Abstract

Objective

To compare the plasma pharmacokinetics of lamivudine 150mg twice daily and 300mg once daily in patients with HIV-1 infection.

Design

Nonblind, sequential, pharmacokinetic study.

Participants

13 patients with HIV-1 infection (median age 36 years).

Methods

Patients were tested during twice daily and then once daily regimens of lamivudine. In both regimens, the total daily dose of lamivudine was identical (300 mg/day). Blood samples for pharmacokinetic analysis were taken over a 12-hour period after ≥7 days of twice daily administration, and again over a 24-hour period after 7 days of once daily administration,.

Results

12 patients completed the study. Lamivudine pharmacokinetic parameters (mean ± SD) after administration of 150mg twice daily were: peak plasma concentration (Cmax) 2077 ± 816 μg/L; trough plasma concentration (Cmin) 332 ±219 μg/L; elimination half-life (t½β) 6.1 ± 1.9h; time to Cmax (tmax) 1.6 ± 0.7h; average concentration over the dosage interval (Cav) 711 ± 269 μg/L; and area under the concentration-time curve (AUC) over 2 dosage intervals (24h) 17 085 ± 6464 μg □h/L. Corresponding values after administration of 300mg once daily were: Cmax3461 ± 854 μg/L; Cmin 146 ± 87 μg/L; t½β 7.9 ± 3.4h; tmax2.2 ± 1.3h; Cav 705 ± 177 μg/L; and AUC over 1 dosage interval (24h) 16 644 ± 4150 μg □ h/L. Statistical analysis showed a significant difference (p < 0.05) between the 2 schedules for Cmax and Cmin values, whereas no significant differences emerged for the other parameters.

Conclusions

Once daily lamivudine leads to a similar exposure in plasma as twice daily administration of the same total daily dose. Since once daily administration may result in improved compliance, these results provide the pharmacokinetic basis for using lamivudine in a once daily regimen. Randomised clinical studies are needed to confirm this pharmacokinetic finding.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Table I
Table II

Similar content being viewed by others

References

  1. Cammack N, Rouse P, Marr CL, et al. Cellular metabolism of (-)-enantiomeric 2′-deoxy-3′-thiacytidine. Biochem Pharmacol 1992 May 28; 43(10): 2059–64

    Article  PubMed  CAS  Google Scholar 

  2. Johnson MA, Moore KHP, Yuen GJ, et al. Clinical pharmaco-kinetics of lamivudine. Clin Pharmacokinet 1999; 36: 41–66

    Article  PubMed  CAS  Google Scholar 

  3. Angel JB, Hussey EK, Hall ST, et al. Pharmacokinetics of 3TC administered with and without food to HIV-infected patients. Drug Invest 1993; 6: 70–4

    Article  Google Scholar 

  4. Moore KHP. Pharmacokinetics (PK) of lamivudine (3-TC) phosphorylation in peripheral blood mononuclear cells (PBMC) from HIV-infected patients [abstract 42470]. 12th International Conference on AIDS; Jun 29-Jul 3 1998; Geneva

  5. Monno L, Cargnel A, Soranzo ML, et al. Comparison of once and twice daily dosing of didanosine in combination with stavudine for the treatment of HIV-1 infection: AI 454-146 Team. Antivir Ther 1999; 4: 195–202

    PubMed  CAS  Google Scholar 

  6. Hoetelmans RM, van Heeswijk RPG, Profijt M, et al. Comparison of the plasma pharmacokinetics and renal clearance of didanosine during once and twice daily dosing in HIV-1 infected individuals. AIDS 1998; 12: F211–16

    Article  PubMed  CAS  Google Scholar 

  7. Zhou XJ, Sommadossi JP. Rapid quantitation of (-)-2′-deoxy-3′-thiacytidine in human serum by high-performance liquid chromatography with ultraviolet detection. J Chromatogr B 1997; 691: 417–24

    Article  CAS  Google Scholar 

  8. Pollard RB. Towards once-daily antiretroviral therapy. AIDS 2000 Nov/Dec; 6: 6. Available from: URL: http://hiv.medscape.com/Medscape/HIV/journal/public/archive/2000/toc-0606.html [Accessed 2001 Jul 25]

  9. Maggiolo F, Migliorino M, Maserati R, et al. Once a day treatment for HIV infection: final 48-week results [abstract 320]. Program and Abstracts of the VIII Conference on Retro-viruses and Opportunistic Infections; Feb 4-8 2001; Chicago

  10. Staszewski S, Haberl A, Carlebach A, et al. Asimple, once-daily dosing regimen for treating HIV-1 infection in intravenous drug users. HIV Med 2000; 1: 162–3

    Article  PubMed  CAS  Google Scholar 

  11. Sension M, Bellos N, Johnson J, et al. Efficacy and safety of switch to 3TC 300 mg QD vs. continued 3TC 150 mg BID in subjects with virologic suppression on stable 3TC/d4T/PI therapy (COLA4005): final 24-week results [abstract 317]. Program and Abstracts of the VIII Conference on Retro-viruses and Opportunistic Infections; Feb 4-8 2001; Chicago

  12. Yuen GJ, Lou Y, Bumgarner NT, et al. Equivalence of plasma and intracellular triphosphate lamivudine pharmacokinetics (PK) following lamivudine (3TC) 300 mg once daily compared to lamivudine 150 mg twice a day in healthy volunteers [abstract P269]. 5th International Congress on Drug Therapy in HIV Infection; Oct 22-26 2000; Glasgow

  13. Moore KHP, Barrett JE, Shaw S, et al. The pharmacokinetics of lamivudine phosphorylation in peripheral blood mono-nuclear cells from patients infected with HIV-1. AIDS 1999; 13: 2239–50

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

We did not receice any grant or support for conducting this study.

Author information

Authors and Affiliations

  1. Division of Infectious and Tropical Diseases, IRCCS San Matteo Hospital, University of Pavia, Pavia, Italy

    Raffaele Bruno, Valentina Ciappina, Paolo Sacchi & Gaetano Filice

  2. Department of Pharmacology, IRCCS San Matteo Hospital, Pavia, Italy

    Mario B. Regazzi, Paolo Villani & Michela Montagna

  3. HIV and Hospital Medical Leader, GSK Italy Medical Directorate, Glaxo Smith Kline Italy, Verona, Italy

    Ruggero Panebianco

Authors
  1. Raffaele Bruno
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mario B. Regazzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Valentina Ciappina
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Paolo Villani
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Paolo Sacchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Michela Montagna
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ruggero Panebianco
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Gaetano Filice
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Raffaele Bruno.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bruno, R., Regazzi, M.B., Ciappina, V. et al. Comparison of the Plasma Pharmacokinetics of Lamivudine During Twice and Once Daily Administration in Patients with HIV. Clin Pharmacokinet 40, 695–700 (2001). https://doi.org/10.2165/00003088-200140090-00005

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003088-200140090-00005

Keywords

Search

Navigation