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 9/2004

01-08-2004 | Review Article

Tenofovir Disoproxil Fumarate

Clinical Pharmacology and Pharmacokinetics

Authors: Dr Brian P. Kearney, John F. Flaherty, Jaymin Shah

Published in: Clinical Pharmacokinetics | Issue 9/2004

Login to get access

Abstract

Tenofovir disoproxil fumarate (tenofovir DF) is an oral prodrug of tenofovir, a nucleotide (nucleoside monophosphate) analogue with activity against retroviruses, including HIV-1, HIV-2 and hepadnaviruses. Following absorption, tenofovir DF is rapidly converted to tenofovir, which is metabolised intracellularly to its active anabolite tenofovir diphosphate, which is a competitive inhibitor of HIV-1 reverse transcriptase and terminates the growing DNA chain. Tenofovir exerts antiviral effects in a variety of cell types, including resting cells.
Tenofovir exhibits longer serum (17 hours) and intracellular (≥60 hours) half-lives than those of nucleoside analogues, which supports a flexible once-daily administration schedule. The pharmacokinetics of tenofovir are dose-proportional and similar in healthy volunteers and HIV-infected individuals. The oral bioavailability of tenofovir is enhanced by administration with a high-fat meal, but is similar at steady state when administered with or without a typical meal.
Tenofovir is not a substrate, inducer or inhibitor of human cytochrome P450 enzymes in vitro or in vivo. Tenofovir DF has been studied with 15 other antiretroviral and other concomitant medications frequently used in the HIV-1-infected population. With the exception of didanosine and atazanavir, which require dosage modifications, no clinically significant drug interactions have been observed with tenofovir DF.
The recommended oral dosage of tenofovir DF in adults is 300 mg/day. Tenofovir is eliminated by renal elimination, including tubular secretion; dose-interval adjustments are necessary for tenofovir DF in patients with significant renal impairment. No dosage adjustment of tenofovir DF is necessary in patients with liver disease.
Footnotes
1
The use of trade names is for product identification purposes only and does not imply endorsement.
 
Literature
1.
Schooley RT, Ruane P, Myers RA, et al. Tenofovir DF in antiretroviral-experienced patients: results from a 48-week, randomized, double-blind study. AIDS 2002 Jun 14; 16(9): 1257–63PubMedCrossRef
2.
Squires K, Pozniak AL, Pierone Jr G, et al. Tenofovir disoproxil fumarate in nucleoside-resistant HIV-1 infection. Ann Intern Med 2003 Sep 2; 139 (5 Pt 1): 313–21PubMed
3.
Staszewski S, Gallant JE, Pozniak AL, et al. Favorable metabolic profile for tenofovir disoproxil fumarate (TDF) versus stavudine (d4T) when used in combination with lamivudine and efavirenz in antiretroviral naive patients: 96-week interim results [abstract]. 2nd International AIDS Society Conference on HIV Pathogenesis and Treatment; 2003 Jul 13–16; Paris
4.
Louie M, Hogan C, Hurley A, et al. Determining the antiviral activity of tenofovir disoproxil fumarate in treatment-naive chronically HIV-1-infected individuals. AIDS 2003; 17(8): 1151–6PubMedCrossRef
5.
Shaw J-P, Sueoka CM, Oliyai R, et al. Metabolism and pharmacokinetics of novel oral prodrugs of 9-[R)-2-(phosphonomethoxy)propyl]denine (PMPA) in dogs. Pharm Res 1997 Dec; 14(12): 1824–9PubMedCrossRef
6.
Van Gelder J, Deferme S, Naesens L, et al. Intestinal absorption enhancement of the ester prodrug tenofovir disoproxil fumarate through modulation of the biochemical barrier by defined ester mixtures. Drug Metab Dispos 2002 Aug; 30(8): 924–30PubMedCrossRef
7.
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 Mar; 42(3): 612–7PubMed
8.
Naesens L, Bischofberger N, Augustijns P, et al. Antiretroviral efficacy and pharmacokinetics of oral bis(isopropyloxy-carbonyloxymethyl)-9-(2-phosphonylmethoxypropyl) adenine in mice. Antimicrob Agents Chemother 1998 Jul; 42(7): 1568–73PubMed
9.
Cundy KC, Sueoka CM, Lynch GR, et al. Pharmacokinetics and bioavailability of the anti-human immunodeficiency virus nucleotide analog 9-[R)-2-(phosphonomethoxy)propyl]denine (PMPA) in dogs. Antimicrob Agents Chemother 1998 Mar; 42(3): 687–90PubMed
10.
Hazra R, Balis FM, Tullio AN, et al. Single-dose and steadystate pharmacokinetics of tenofovir DF in HIV-infected children. Antimicrob Agents Chemother 2003 Jan; 48(1): 124–9CrossRef
11.
Deeks SG, Barditch-Crovo P, Lietman PS, et al. Safety, pharmacokinetics, and antiretroviral activity of intravenous 9-[2-(R)-(phosphonomethoxy)propyl]adenine, a novel antihumanimmunodeficiency virus (HIV) therapy, in HIV-infected adults. Antimicrob Agents Chemother 1998 Sep; 42(9): 2380–4PubMed
12.
Naesens L, Baizarini J, Bischofberger N, et al. Antiretroviral activity and pharmacokinetics in mice of oral bis(pivaloylox-ymethyl)-9-(2-phosphonylmethoxyethyl)adenine, the bis(pivaloyoxymethyl) ester prodrug of 9-(2-phosphonylmethoxyethyl)adenine. Antimicrob Agents Chemother 1996 Jan; 40(1): 22–8PubMed
13.
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 HIV-1 infected adults. Antimicrob Agents Chemother 2001 Oct; 45(10): 2733–9PubMedCrossRef
14.
Pozniak AL, Plettenberg A, Rozenbaum W, et al. Tenofovir DF: a 24-week interim analysis from a phase III randomized, double blind, placebo controlled study in antiretroviral experienced patients [abstract]. 8th European Conference on Clinical Aspects and Treatment of HIV-Infection; 2001 Oct 28–31; Athens
15.
Hawkins T, Veikley W, St Claire R, et al. Intracellular pharmacokinetics of tenofovir-DP and carbovir-TP in patients receiving triple nucleoside regimens [oral presentation]. 5th International Workshop on Clinical Pharmacology of HIV Therapy; 2004 Apr 1–3; Rome
16.
Kearney BP, Damle B, Plummer A, et al. Pharmacokinetic evaluation of tenofovir DF and enteric-coated didanosine. XIV International AIDS Conference; 2002 Jul 7–12; Barcelona
17.
Gilead Sciences Inc. Tenofovir disoproxil fumarate (Viread®) tablets: prescribing information. Foster City (CA): Gilead Sciences Inc., 2003 Oct
18.
Kearney BP, Gill SC, Flaherty JF, et al. Effect of demographic variables on the pharmacokinetics of tenofovir DF in HIV-infected patients and healthy subjects [poster]. 41st Interscience Conference on Antimicrobial Agents and Chemotherapy; 2001 Dec 16–19; Chicago
19.
Kearney BP, Liaw S, Yale K, et al. Pharmacokinetics following single dose administration of tenofovir DF in subjects with renal impairment [poster]. Sixth International Congress on Drug Therapy in HIV Infection; 2002 Nov 17–21; Glasgow
20.
Kearney BP, Benhamou Y, Flaherty J, et al. Tenofovir pharmacokinetics in hepatic impairment and drug interaction potential with agents used to treat viral hepatitis [poster]. 11th Conference on Retroviruses and Opportunistic Infections; 2004 Feb 8–11; San Francisco
21.
Flaherty JF, Kearney BP, Wolf JJ, et al. A multiple-dose, randomized, crossover drug interaction study between tenofovir DF and efavirenz, indinavir, or lopinavir/ritonavir [poster]. The 1st IAS Conference on HIV Pathogenesis and Treatment; 2001 Jul 8–11; Buenos Aires
22.
Kearney BP, Mittan A, Sayre J, et al. Pharmacokinetic drug interaction and long term safety profile of tenofovir DF and lopinavir/ritonavir [poster]. 43rd Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2003 Sep 14–17; Chicago
23.
Kearney BP, Flaherty JF, Sayre JR, et al. A multiple-dose, randomized, crossover drug interaction study between tenofovir DF and lamivudine or didanosine. The 1st IAS Conference on HIV Pathogenesis and Treatment; 2001 Jul 8–11; Buenos Aires
24.
Kearney BP, Isaacson E, Sayre J, et al. Didanosine and tenofovir DF drug-drug interaction: assessment of didanosine and dose reduction [poster]. 10th Conference on Retroviruses and Opportunistic Infections; 2003 Feb 10–14; Boston
25.
Kaul S, Damle B, Bassi K, et al. Pharmacokinetic evaluation of reduced doses of didanosine enteric coated capsules (ddI-EC) in combination with tenofovir disoproxil fumarate (TDF) and food for a once-daily antiretroviral regimen [poster]. 4th International Workshop on Clinical Pharmacology of HIV Therapy; 2003 Mar 27–29; Cannes
26.
Ray A, Olson L, Fridland A. Mechanism of the drug interactions between 2′,3′-dideoxyinosine and allopurinol, ganciclovir or tenofovir [poster]. 5th International Workshop on Clinical Pharmacology of HIV Therapy; 2004 Apr 1–3; Rome
27.
Ray A, Olson L, Fridland A. Role of purine nucleoside Phosphorylase in drug interactions between 2′,3′-dideoxyinosine and allopurinol, ganciclovir or tenofovir. Antimicrob Agents Chemother 2004 Apr; 48(4): 1089–95PubMedCrossRef
28.
Flaherty J, Kearney B, Wolf J, et al. Coadministration of tenofovir DF and didanosine: a pharmacokinetic and safety evaluation [poster]. 41st Interscience Conference on Antimicrobial Agents and Chemotherapy; 2001 Dec 16–19; Chicago
29.
Kearney BP, Flaherty JF, Wolf JJ, et al. Coadministration of tenofovir DF and didanosine: pharmacokinetic drug-drug interaction and safety evaluation [poster 172]. 8th European Conference on Clinical Aspects and Treatment of HIV Infection; 2001 Oct 28–31; Athens
30.
Robbins BL, Wilcox CK, Fridland A, et al. Metabolism of tenofovir and didanosine in quiescent or stimulated human peripheral blood mononuclear cells. Pharmacotherapy 2003 Jun; 23(6): 695–701PubMedCrossRef
31.
Blum MR, Begley J, Zong J, et al. Lack of a pharmacokinetic interaction between emtricitabine and tenofovir DF when coadministered to steady state in healthy volunteers [poster]. 43rd Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2003 Sep 14–17; Chicago
32.
33.
Kearney BP, Zong J, Begley J, et al. Bioequivalence of combination tenofovir DF/emtricitabine tablets for one-pill once daily administration [poster]. 5th International Workshop on Clinical Pharmacology of HIV Therapy; 2004 Apr 1–3; Rome
34.
Kaul S, Bassi K, Damle B, et al. Stavudine extended release formulation (D4T XR) and tenofovir disoproxil fumarate (TDF): lack of a pharmacokinetic (PK) drug interaction [abstract]. 11th Conference on Retroviruses and Opportunistic Infections; 2004 Feb 8–11; San Francisco
35.
Kaul S, Bassi K, Damle B, et al. Lack of interaction between stavudine extended release formulation (d4T XR) and tenofovir disoproxil fumarate (TDF) [abstract]. 10th Conference on Retroviruses and Opportunistic Infections; 2003 Feb 10–14; Boston
36.
Kearney BP, Isaacson E, Sayre J, et al. The pharmacokinetics of abacavir, a purine nucleoside analogue, are not affected by tenofovir DF [poster]. 43rd Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2003 Sep 14–17; Chicago
37.
Farthing C, Khanlou H, Yeh V. Early virologic failure in a pilot study evaluating the efficacy of abacavir, lamivudine and tenofovir in the treatment naive HIV-infected patients [abstract]. Antivir Ther 2003; 8 Suppl. 1: S195
38.
Gallant JE, Rodriguez A, Weinberg W, et al. Early non-response to tenofovir DF (TDF) + abacavir (ABC) and lamivudine (3TC) in a randomized trial compared to efavirenz (EFV) + ABC and 3TC: ESS30009 unplanned interim analysis [oral presentation]. 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy; 2003 Sep 14–17; Chicago
39.
Ray A, Vela JE, Olson L, et al. Lack of interaction between tenofovir and abacavir in human cells [poster]. 5th International Workshop on Clinical Pharmacology of HIV Therapy; 2004 Apr 1–3; Rome
40.
Kearney BP, Flaherty JF, Wolf J, et al. Lack of clinically relevant drug-drug interactions between tenofovir DF and efavirenz, indinavir, lamivudine and lopinavir/ritonavir in healthy subjects [poster]. 8th European Conference on Clinical Aspects and Treatment of HIV Infection; 2001 Oct 28–31; Athens
41.
DeJesus E, Grinsztejn B, Rodriguez C, et al. Efficacy and safety of atazanavir (ATV) with ritonavir (RTV) or saquinavir (SQV) vs lopinavir/ritonavir (LPV/RTV) in patients who have experienced virologic failure on multiple HAART regimens: 48-week results from BMS AI424-045 [abstract]. 11th Conference on Retroviruses and Opportunistic Infections; 2004 Feb 8–11; San Francisco
42.
Gathe J, Podzamczer D, Johnson M, et al. Once-daily vs twice-daily lopinavir/ritonavir in antiretroviral-naîve patients: 48-week results [poster]. 11th Conference on Retroviruses and Opportunistic Infections; 2004 Feb 8–11; San Francisco
43.
44.
Chiu Y-L, Foit C, Gathe J, et al. Multiple-dose pharmacokinetics and initial antiviral effect of once daily lopinavir/ritonavir (LPV/r) in combination with tenofovir (TDF) and emtricitabine (FTC) in HIV-infected antiretroviral-naîve subjects (study 418) [poster]. Second IAS Conference on HIV Pathogenesis and Treatment; 2003 Jul 13–16; Paris
45.
Kaul S, Bassi K, Damle, et al. Pharmacokinetic (PK) evaluation of the combination of atazanavir (ATV), enteric coated didanosine (ddI-EC), and tenofovir disoproxil fumarate (TDF) for a once-daily antiretroviral regimen [abstract]. 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy; 2003 Sep 14–17; Chicago
46.
Kruse G, Stocker H, Breske A, et al. Trough levels of seven different atazanavir regimens in HIV-infected patients [poster]. 5th International Workshop on Clinical Pharmacology of HIV Therapy; 2004 Apr 1–3; Rome
47.
Taburet A-M, Piketty C, Chazallon C, et al. Interactions between atazanavir-ritonavir and tenofovir in heavily pretreated human immunodeficiency virus-infected patients. Antimicrob Agents Chemother 2004 Jun; 48(6): 2091–6PubMedCrossRef
48.
49.
Boffito M, D’Avolio A, Di Perri G, et al. Repeated pharmacokinetics of tenofovir disoproxil fumarate (TDF) in HIV-infected adults receiving saquinavir (SQV) hard gel/ritonavir (RTV) 1000/l00mg BID [poster]. 5th International Workshop on Clinical Pharmacology of HIV Therapy; 2004 Apr 1–3; Rome
50.
Ananworanich J, Siangphoe U, Mahanontharit A, et al. Saquinavir Crmin before and after switching NRTI to tenofovir in patients treated with once-daily saquinavir hard gel capsule/ritonavir 1600 mg/100mg [poster]. 5th International Workshop on Clinical Pharmacology of HIV Therapy; 2004 Apr 1–3; Rome
51.
Smith P, Kearney BP, Cloen D, et al. Tenofovir DF does not affect the pharmacokinetics of pharmacodynamics of methadone. Pharmacotherapy. In press
52.
Kearney BP, Isaacson E, Sayre J, et al. Tenofovir DF (TDF) and norgestimate/ethinyl estradiol: lack of pharmacokinetic drug interaction [poster]. 43rd Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2003 Sep 14–17; Chicago
53.
Droste JAH, Kearney BP, Horssen P, et al. Lack of clinically relevant interaction between tenofovir DF and rifampin in healthy volunteers [poster]. 5th International Workshop on Clinical Pharmacology of HIV Therapy; 2004 Apr 1–3; Rome
54.
Izzedine H, Isnard-Bagnis C, Hulot J-S, et al. Renal safety of tenofovir in HIV treatment-experienced patients. AIDS 2004 Apr 20; 18(7): 1074–6PubMedCrossRef
55.
Squires K, Pozniak AL, Pierone G, et al. Tenofovir DF in antiretroviral-experienced, nucleoside-resistant HIV-1 infected patients with incomplete viral suppression. Ann Intern Med 2003; 139(5): 313–20PubMed
56.
Gallant JE, Pozniak AL, Staszewski S, et al. Similar 96 week renal safety profile of tenofovir disoproxil fumarate vs stavudine when used in combination with lamivudine and efavirenz in antiretroviral-naîve patients [poster H-840]. 43rd Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 2003 Sep 14–17; Chicago
57.
Schooley RT, Ruane P, Myers RA, et al. Tenofovir DF in antiretroviral-experienced patients: results from a 48-week, randomized, double-blind study. AIDS 2002; 16(9): 1257–63PubMedCrossRef
Metadata
Title
Tenofovir Disoproxil Fumarate
Clinical Pharmacology and Pharmacokinetics
Authors
Dr Brian P. Kearney
John F. Flaherty
Jaymin Shah
Publication date
01-08-2004
Publisher
Springer International Publishing
Published in
Clinical Pharmacokinetics / Issue 9/2004
Print ISSN: 0312-5963
Electronic ISSN: 1179-1926
DOI
https://doi.org/10.2165/00003088-200443090-00003