Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Clinical Pharmacokinetics
Published in: Clinical Pharmacokinetics 14/2003

01-12-2003 | Leading Article

Once-Daily Administration of Antiretrovirals

Pharmacokinetics of Emerging Therapies

Authors: Dr Anne-Marie Taburet, Sabine Paci-Bonaventure, Gilles Peytavin, Jean-Michel Molina

Published in: Clinical Pharmacokinetics | Issue 14/2003

Login to get access

Abstract

Adherence to therapy is of critical importance for the long-term success of the treatment of HIV infection. Once-daily administration of antiretroviral agents is appealing, as it may increase patient’s adherence. The pharmaceutical industry is making huge efforts to develop drugs or combinations of drugs with pharmacokinetic properties allowing once-daily administration. The major pharmacokinetic requirement for once-daily administration is that the intracellular concentration of the antiretroviral or its active metabolite remains above the minimal concentration that can inhibit viral replication during the entire 24-hour period. Soon, all three major classes of antiretroviral agents will be available as once-daily formulations. However, only a few clinical trials have yet assessed the efficacy and safety of truly once-daily antiretroviral combinations. Preliminary results from these small pilot studies suggest that once-daily administration of antiretrovirals is a feasible approach. Large comparative trials are needed before the real benefits of such a strategy can be fully assessed.
Literature
1.
Carpenter CC, Cooper DA, Fischl MA, et al. Antiretroviral therapy in adults: updated recommendations of the International AIDS Society-USA panel. JAMA 2000; 283: 381–90PubMedCrossRef
2.
Hogg RS, Heath KV, Yip B, et al. Improved survival among HIV-infected individuals following initiation of antiretroviral therapy. JAMA 1998; 279: 450–4PubMedCrossRef
3.
Haubrich RH, Little SJ, Currier JS, et al. The value of patientreported adherence to antiretroviral therapy in predicting virologic and immunologic response. AIDS 1999; 13: 1099–107PubMedCrossRef
4.
Carr A, Samaras K, Thorisdottir A, et al. Diagnosis, prediction, and natural course of HIV-1 protease-inhibitor-associated lipodystrophy, hyperlipidaemia, and diabetes mellitus: a cohort study. Lancet 1999; 353: 2093–8PubMedCrossRef
5.
Ena J, Pasquau F. Once-a-day highly active antiretroviral therapy: a systematic review. Clin Infect Dis 2003; 36(9): 1186–90PubMedCrossRef
6.
7.
Rosenbach KA, Allison R, Nadler JP. Daily dosing of highly active antiretroviral therapy. Clin Infect Dis 2002; 34: 686–92PubMedCrossRef
8.
Boyle BA. Efficacy and safety of once-daily antiretroviral therapy. AIDS Read 2002; 12(3): 90–6PubMed
9.
10.
Paterson DL, Swindells S, Mohr J, et al. Adherence to protease inhibitor therapy and outcomes in patients with HIV-infection. Ann Intern Med 2000; 1333: 21–30
11.
Ostrop NJ, Hallett KA, Gill MJ. Long-term patient adherence to antiretroviral therapy. Ann Pharmacother 2000 Jun; 34(6): 703–9PubMedCrossRef
12.
Duran S, Savés M, Spire B, et al. Failure to maintain long-term adherence to highly active antiretroviral therapy: the role of lipodystrophy. AIDS 2001; 15: 2441–4PubMedCrossRef
13.
Paes A, Bakker A, Soe-Agnie C. Impact of dosage frequency on patient compliance. Diabetes Care 1997; 20: 1512–7PubMedCrossRef
14.
Sanchez-Navarro A, Sanchez Recio MM. Basis of anti-infective therapy: pharmacokinetic-pharmacodynamic criteria and methodology for dual dosage individualisation. Clin Pharmacokinet 1999 Oct; 37(4): 289–304PubMedCrossRef
15.
Becker S, Fisher A, Flexner C, et al. Pharmacokinetic parameters of protease inhibitors and the Cmin/IC50 ratio: call for consensus. J Acquir Immune Defic Syndr 2001; 27: 210–1PubMed
16.
Arts EJ, Wainberg MA. Mechanism of nucleoside analog antiviral activity and resistance during human immunodeficiency virus reverse transcription. Antimicrob Agents Chemother 1996; 40: 527–40PubMed
17.
Robbins BL, Srinivas RV, Kim C, et al. Anti-human immunodeficiency virus activity and cellular metabolism of a potential prodrug of the acyclic nucleoside phosphonate 9-R-(2-phosphonomethoxypropyl) adenine (PMPA), bis (isopropyloxymethylcarbonyl) PMPA. Antimicrob Agents Chemother 1998; 42: 612–7PubMed
18.
Barry M, Mulcahy F, Merry C, et al. Pharmacokinetics and potential interactions amongst antiretroviral agents used to treat patients with HIV infection. Clin Pharmacokinet 1999; 36: 289–304PubMedCrossRef
19.
Parang K, Wiebe LI, Knaus EE. Novel approaches for designing 5′-O-ester prodrugs of 3′-azido-2′,3′-dideoxythymidine (AZT) [abstract 10]. Curr Med Chem 2000; 7: 995–1039PubMedCrossRef
20.
Girard PM, Pegram PS, Diquet B, et al. Phase II placebo-controlled trial of fozivudine tidoxil for HIV infection: pharmacokinetics, tolerability, and efficacy [abstract 15]. J Acquir Immune Defic Syndr 2000; 23: 227–35PubMed
21.
Evans W, Schentag JJ, Jusko WJ. Applied pharmacokinetics: principles of therapeutic drug monitoring. Vancouver (WA): Applied Therapeutics Inc, 1992
22.
Gourlay GK. Sustained relief of chronic pain; pharmacokinetics of sustained release morphine. Clin Pharmacokinet 1998; 35: 173–90PubMedCrossRef
23.
Kaul S, Damie B, Gale J, et al. Pharmacokinetics (PK) of stavudine (d4t) extended release formulation compared with stavudine immediate release (IR) formulation as part of potent antiretroviral combination therapy [abstract 430W]. 9th Conference on Retroviruses and Opportunistic Infections; 2002 Feb 24–28; Seattle (WA)
24.
Benghuzzi H. Long-term sustained delivery of 3′-azido-2′,3′-dideoxythymidine in vivo by means of HA and TCP delivery devices. Biomed Sci Instrum 2000; 36: 343–8PubMed
25.
Cunningham RF, Israili ZH, Dayton PG. Clinical pharmacokinetics of probenecid. Clin Pharmacokinet 1981 Mar–Apr; 6(2): 135–51PubMedCrossRef
26.
Dresser GK, Spence JD, Bailey DG. Pharmacokinetic-pharma-codynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition. Clin Pharmacokinet 2000; 38: 41–57PubMedCrossRef
27.
Cooper CL, van Heeswijk RPG, Gallicano K, et al. A review of low dose ritonavir in protease inhibitor combination therapy. Clin Infect Dis 2003; 36: 1585–92PubMedCrossRef
28.
Hoetelmans RMW, van Heeswijk RPG, Profijt M, et al. Comparison of the plasma pharmacokinetics and renal clearance of didanosine during once and twice daily in HIV-1 infected individuals. AIDS 1998; 12: F211–6PubMedCrossRef
29.
Yuen G, Lou Y, Bumgarner NT, et al. Equivalence of plasma and intracellular triphosphate lamivudine pharmacokinetics following lamivudine 300mg once daily compared to lamivudine 150mg twice a day in healthy volunteers. Program and Abstracts of the 5th International Congress on Drug Therapy in HIV infection; 2000 Oct 22–26; Glasgow, UK
30.
Bruno R, Regazzi MB, Ciappina V, et al. Comparison of the plasma pharmacokinetics of lamivudine during twice and once daily administration in patients with HIV. Clin Pharmacokinet 2001; 40(9): 695–700PubMedCrossRef
31.
Van Heeswijk RP, Veldkamp AL, Mulder JW, et al. The steady-state pharmacokinetics of nevirapine during once daily and twice daily dosing in HIV-1-infected individuals. AIDS 2000; 14: F77–82PubMedCrossRef
32.
Kazatchkine MD, Ngo Van P, Costagliola D, et al. Didanosine dosed once daily is equivalent to twice daily dosing for patients on double or triple combination antiretroviral therapy. J Acquir Immune Defic Syndr 2000; 24: 418–24PubMed
33.
34.
Kearney BP, Isaacson E, Sayre J, et al. Didanosine and tenofovir DF drug-drug interaction: assessment of didanosine dose reduction [abstract no. 533]. The 10th CROI; 2003 Feb 10–14; Boston.
35.
36.
Barrios I, Maida L, Pérez-Saleme E, et al. Safety and efficacy of combinations based on didanosine 400 mg od plus tenofovir 300 mg od [abstract H-847]. 43rd ICAAC; 2003 Sep 14–17; Chicago
37.
Sension MG, Beilos NC, Johnson J, et al. Lamivudine 300mg vs continued lamivudine 150mg BID with stavudine and a protease inhibitor in suppressed patients. HIV Clin Trials 2002; 3(5): 361–70PubMedCrossRef
38.
Harris M, Back D, Kewn S, et al. Intracellular carbovir triphosphate levels in patients taking abacavir once a day. AIDS 2002; 16(8): 1196–7PubMedCrossRef
39.
Pollard R, Ive P, Whelden M, et al. Stavudine XR vs Stavudine IR as part as potent antiretroviral combination therapy: 24-week safety and antiviral efficacy (BMS 099) [abstract 411W]. 9th Conference on Retroviruses and Opportunistic Infections; 2002 Feb 24–28; Seattle (WA)
40.
Delehanty J, Kahn J, Thompson M, et al. Selection of FTC dose based on viral kinetics and pharmacokinetics in an accelerated clinical trial design [abstract 12208]. Conference Records of the 12th World AIDS Conference; 1998 Jun 28–Jul 3; Geneva.
41.
Barditch-Crovo P, Deeks SG, Collier A, et al. Phase I/II trial of the pharmacokinetics, safety, and antiretroviral activity of tenofovir disoproxil fumarate in human immunodeficiency virus-infected adults. Antimicrob Agents Chemother 2001; 45: 2733–9PubMedCrossRef
42.
Squires K, Pozniak AL, Pierone G, et al. Study 907 Team. Tenofovir disoproxil fumarate in nuceolside-resistant HIV-1 infection: a randomized trial. Ann Intern Med 2003; 139: 313–20PubMed
43.
Taburet AM, Piketty C, Gérard I, et al. Pharmacokinetic parameters of atazanavir/ritonavir when combined to tenofovir in HIV infected patients with multiple treatment failures: a substudy of Puzzle2-ANRS 107 Trial [abstract no. 357]. The 10th CROI; 2003 Feb 10–14; Boston
44.
Kaul K, Bassi B, Damle J, et al. Pharmacokinetic evaluation of the combination of atazanavir (ATV), enteric coated didanosine (ddI-EC), and tenofovir disoproxil fumarate (TDF) for a once-daily antiretroviral regimen [abstract A-1616]. 43rd ICAAC; 2003 Sep 14–17; Chicago
45.
Kearney BP, Mittan A, Sayre J, et al. Pharmacokinetic drug interaction and long term safety profile of tenofovir DF and lopinavir/ritonavir [abstract A-1617]. 43rd ICAAC; 2003 Sep 14–17; Chicago
46.
Kaul K, Bassi B, Damle R, et al. Lack of interaction between stavudine extended-release formulation and tenofovir disproxil fumarate [abstract no. 534]. The 10th CROI; 2003 Feb 10–14; Boston
47.
Blum MR, Begley J, Zong J, et al. Lack of pharmacokinetic interaction between emtricitabine and tenofovir DF when coadministered to steady state in healthy volunteers [abstract A-1621]. 43rd ICAAC; 2003 Sep 14–17; Chicago
48.
Kearney BP, Isaacson E, Sayre J, et al. The pharamcokinetics of abacavir, a purine nucleoside analog, are not affected by tenofovir DF [abstract A-1615]. 43rd ICAAC; 2003 Sep 14–17; Chicago
49.
50.
51.
Staszewski S, Morales-Ramirez J, Tashima KT, et al. Efavirenz plus zidovudine and lamivudine, efavirenz plus indinavir, and indinavir plus zidovudine and lamivudine in the treatment of HIV-1 infection in adults. N Engl J Med 1999; 341: 1865–73PubMedCrossRef
52.
Marzolini C, Telenti A, Decosterd LA, et al. Efavirenz plasma levels can predict treatment failure and central nervous system side effects in HIV-1-infected patients. AIDS 2001 Jan 5; 15(1): 71–5PubMedCrossRef
53.
Lopez-Cortes LF, Ruiz-Valderas R, Viciana P, et al. Pharmacokinetic interaction between efavirenz and rifampicin in HIV-infected patients with tuberculosis. Clin Pharmacokinet 2002; 41(9): 681–90PubMedCrossRef
54.
Raffi F, Reliquet V, Ferre V, et al. The Virgo study: nevirapine, didanosine and stavudine combination therapy in antiretroviral naive HIV-1 infected adults. Antivir Ther 2000; 5: 267–72PubMed
55.
Aarnoutse RE, Droste JA, van Oosterhout JJ, et al. Pharmacokinetics, food intake requirements and tolerability of once-daily combinations of nelfinavir and low-dose ritonavir in healthy volunteers. Br J Clin Pharmacol 2003; 55(2): 115–25PubMedCrossRef
56.
Moyle GJ, Back D. Principle and practice of HIV-protease inhibitor pharmacoenhancement. HIV Med 2001; 2: 105–13PubMedCrossRef
57.
58.
Acosta EP, Kakuda TN, Brundage RC, et al. Pharmaco-dynamics of human immunodeficiency virus type 1 protease inhibitors. Clin Infect Dis 2000; 30 Suppl. 2: S151–9PubMedCrossRef
59.
Eron J, Bernstein B, King M, et al. Once-daily vs twice-daily Kaletra (lopinavir/ritonavir) in antiretroviral-naive HIV+ patients: 48-week follow up [abstract 409W]. 9th Conference on Retroviruses and Opportunistic Infections; 2002 Feb 24–28; Seattle
60.
Wood R, Trepo C, Livrozet JM, et al. Amprenavir 600mg/ ritonavir 100mg bid or amprenavir 1200mg/ritonavir 200mg qd given in combination with abacavir and lamivudine maintains efficacy in ART-nalve HIV-1 infected adults over 12 weeks (APV20001) [abstract 332]. Programs and abstracts of the 8th Conference on Retroviruses and Opportunistic Infections; 2001 Feb 4–8; Chicago (IL)
61.
Mallolas J, Blanco JL, Sarasa M, et al. Dose-finding study of once-daily indinavir/ritonavir plus zidovudine and lamivudine in HIV-infected patients. J Acquir Immune Defic Syndr 2000; 25: 229–35PubMedCrossRef
62.
Kilby JM, Sfakianos G, Gizzi N, et al. Safety and pharmacokinetics of once-daily regimens of soft-gel capsule saquinavir plus minidose ritonavir in human immunodeficiency virusnegative adults. Antimicrob Agents Chemother 2000; 44: 2672–8PubMedCrossRef
63.
Van Heeswijk RP, Veldkamp AI, Mulder JW, et al. Once-daily dosing of saquinavir and low-dose ritonavir in HIV-1-infected individuals: a pharmacokinetic pilot study. AIDS 2000; 14: F103–10PubMedCrossRef
64.
Cardiello PG, Van Heeswijk RP, Hassink EA, et al. Simplifying protease inhibitor therapy with once-daily dosing of saquinavir soft-gelatin capsules/ritonavir (1600/100 mg): HIVNAT 001.3 study. J Acquir Immune Defic Syndr 2002; 29: 464–70PubMed
65.
Hsyu PH, Lewis RH, Tran JQ, et al. Pharmacokinetics of nelfinavir after once daily dosing in combination with minidoses of ritonavir in healthy subjects. Poster LbPeB7049.13th International AIDS Conference; 2000 Jul 9–14; Durban
66.
O’Mara E, Mummaneni V, Bifano M, et al. Steady-state pharmacokinetic interaction study between BMS-232632 and ritonavir in healthy subjects [abstract 740]. Programs and abstracts of the 8th Conference on Retroviruses and Opportunistic Infections; 2001 Feb 4–8; Chicago (IL)
67.
Sadler BM, Stein DS. Clinical pharmacology and pharmacokinetics of amprenavir. Ann Pharmacother 2002; 36: 102–18PubMedCrossRef
68.
Khoo SH, Gibbons SE, Back DJ. Therapeutic drug monitoring as a tool in treating HIV infection. AIDS 2001; 15 Suppl. 5: S171–81PubMedCrossRef
69.
Sanne I, Piliero P, Squires K, et al. AI424-007 Clinical Trial Group. Results of a phase 2 clinical trial at 48 weeks (AI424-007): a dose-ranging, safety, and efficacy comparative trial of atazanavir at three doses in combination with didanosine and stavudine in antiretroviral-naiive subjects. J Acquir Immune Defic Syndr 2003; 32(1): 18–29PubMedCrossRef
70.
71.
Mole L, Schmidgall D, Holodniy M. A pilot trial of indinavir, ritonavir, didanosine, and lamivudine in a once a day four drug regimen for HIV infection. J Acquir Immune Defic Syndr 2001; 27: 260–5PubMed
72.
Hsieh SM, Hung CC, Lu PL, et al. Preliminary experience of adverse drug reactions, tolerability and efficacy of a once-daily regimen of antiretroviral combination therapy. J Acquir Immune Defic Syndr 2000; 24: 287–8PubMed
73.
Staszewski S, Haberl A, Gute P, et al. Nevirapine/didanosine/ lamivudine once-daily in HIV-1-infected intravenous drug users. Antivir Ther 1998; 3 Suppl. 4: 55–6PubMed
74.
Maggiolo F, Migliorino M, Maserati R, et al. Virological and immunological response to a once a day antiretroviral regimen with didanosine, lamivudine and efavirenz. AntivirTher 2001; 6: 249–53
75.
Molina JM, Ferchal F, Rancinan C, et al. Once-daily therapy with emtricitabine, didanosine and efavirenz in human immunodeficiency virus-infected patients. J Infect Dis 2000; 182: 599–602PubMedCrossRef
76.
Landman R, Schiemann R, Thiam S, et al. Once-a-day higly active antiretroviral therapy in treatment-naiive HIV-1-infected adults in Senegal. AIDS 2003; 17(7): 1017–22PubMedCrossRef
77.
Molina JM, Rancinan C, Ferchal F, et al. Once-daily combination therapy with emtricitabine, didanosine and efavirenz in treatment-naive HIV-infected adults: 64-week follow-up of the ANRS 091 trial [abstract 321]. In: Programs and abstracts of the 8th Conference on Retroviruses and Opportunistic Infections; 2001 Feb 4-8; Chicago (IL)
78.
Veldkamp AI, Harris M, Montaner JSG, et al. The steady state pharmacokinetics of efavirenz and nevirapine when used in combination in human immunodeficiency virus type 1-infected persons. J Infect Dis 2001; 184: 37–42PubMedCrossRef
79.
Gazzard G, Dejesus E, Cahn P, et al. Abacavir (ABC) once daily (OAD) plus lamivudine (3TC) OAD in combination with efavirenz (EFV) OAD is well tolerated and effective in the treatment of antiretroviral therapy (ART) naiive adults with HIV-1 infection (ZODIAC study: CNA30021) [abstract H-1722b]. 43rd ICAAC; 2003 Sep 14–17; Chicago
80.
Molina JM, Ferchal F, Journot V, et al. Emtricitabine, didanosine, and efavirenz once daily versus continued PI-based HAART in HIV-infected adults with undetectable plasma HIV-RNA: 48-week results of a prospective randomised multicentre trial (ALIZE-ANRS99) [abstract no 37]. 2nd IAS conference on HIV pathogenesis and treatment, 2003 Jul 13–16; Paris
81.
Gallant JE, Rodriguez AE, Weinberg W, et al. Early nonresponse to tenofovir DF (TDF) + abacavir (ABC) and lamivudine (3TC) in a randomised trial compared to efavirenz (EFV) + ABC and 3TC: ESS30009 unplanned interim analysis [abstract H-1722a]. 43rd ICAAC; 2003 Sep 14–17; Chicago
82.
Hoggard PG, Back DJ. Intracellular pharmacology of nucleoside analogues and protease inhibitors: role of transporter molecules. Curr Opin Infect Dis 2002; 15: 3–8PubMedCrossRef
83.
Back D, Gatti G, Fletcher C, et al. Therapeutic drug monitoring in HIV-infection: current status and future directions. AIDS 2002; 16: S5–37PubMedCrossRef
Metadata
Title
Once-Daily Administration of Antiretrovirals
Pharmacokinetics of Emerging Therapies
Authors
Dr Anne-Marie Taburet
Sabine Paci-Bonaventure
Gilles Peytavin
Jean-Michel Molina
Publication date
01-12-2003
Publisher
Springer International Publishing
Published in
Clinical Pharmacokinetics / Issue 14/2003
Print ISSN: 0312-5963
Electronic ISSN: 1179-1926
DOI
https://doi.org/10.2165/00003088-200342140-00001

Other articles of this Issue 14/2003

Clinical Pharmacokinetics 14/2003 Go to the issue

Original Research Article

Pharmacokinetics of Pimecrolimus, a Novel Nonsteroid Anti-Inflammatory Drug, After Single and Multiple Oral Administration

Review Article

Principles and Clinical Application of Assessing Alterations in Renal Elimination Pathways

Review Article

Clinical Pharmacokinetics of Drugs Used to Treat Urge Incontinence

Review Article

Transdermal Penetration of Topical Drugs Used in the Treatment of Acne

Review Article

Pharmacology of Anticancer Drugs in the Elderly Population