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Drug Class: Microbicides
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Drug Description |
| Tenofovir is an adenosine nucleoside monophosphate reverse transcriptase inhibitor and viral replication inhibitor.[1] |
HIV/AIDS-Related Uses |
| Tenofovir gel, also known as PMPA gel, is being investigated in Phase II monotherapy studies as a vaginal microbicide for the prevention of HIV transmission. Tenofovir is also being studied in combination with PRO 2000, another investigational vaginal microbicide.[2][3] Approved oral formulations of its prodrug, tenofovir disoproxil fumarate (tenofovir DF), are used to treat HIV.[4] |
Non HIV/AIDS-Related Uses |
| In vitro testing of tenofovir demonstrated antiviral activity against hepatitis B virus (HBV).[5][6] Tenofovir disoproxil fumarate, the orally bioavailable prodrug of tenofovir, is being evaluated in HBV/HIV coinfected patients who developed HBV breakthrough during treatment with lamivudine.[7] |
Dosing Information |
Mode of Delivery |
| Intravaginal.[8] |
Dosage Form |
Tenofovir gel is available in 0.3% and 1% concentrations. In clinical studies, it is applied vaginally once or twice daily. Precoital applications are also being investigated.[9]
Tenofovir gel is packaged in 6-gram tubes and in 4-gram, single-dose applicators.[10] |
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Pharmacology |
Tenofovir, a nucleotide analogue, is characterized by its ability to enter and inhibit viral replication in HIV infected, HIV uninfected, and resting cells, thus forming active drug reservoirs.[11]
Tenofovir has a long intracellular half-life.[12] Serum plasma concentrations with tenofovir gel application have ranged from 3 to 25.8 ng/ml, remaining lower than the 50 ng/ml minimum plasma concentration achieved with oral tenofovir DF.[13]
Animal studies support the use of tenofovir gel as a microbicide. One small study of tenofovir gel administed vaginally to four macaques resulted in 100% protection, compared with observed HIV transmission in two macaques administered placebo gel.[14]
HPTN 050, an open-label, Phase I trial, evaluated tenofovir 0.3% and 1% gels, administered daily or twice-daily for 2 weeks in sexually abstinent HIV infected and HIV uninfected women to determine toxicity, pharmacokinetics, and gel acceptability. Fourteen of 25 women (56%) experienced low but detectable serum tenofovir levels. Asymptomatic bacterial vaginosis in 29 women resolved in 14 (48%) after gel administration. No new resistance mutations evolved, and no patients had high-level tenofovir mutations, such as K65R.[15][16]
HPTN 059 is an ongoing, multicenter, randomized, Phase II trial in HIV uninfected women to determine the safety and acceptability of tenofovir 1% gel administered over 24 weeks with a 48-week follow-up. Patients will be assigned to one of four cohorts: tenofovir 1% daily; placebo daily; tenofovir 1%, coitally dependent; or placebo, coitally dependent.[17] |
Adverse Events/Toxicity |
In an open-label, Phase I trial to evaluate tenofovir 0.3% and 1% gel concentrations in HIV uninfected and HIV infected women, the gel was well tolerated. Although 92% of patients experienced at least one adverse effect, 87% were mild and 70% were genitourinary. Thirty-two percent of patients experienced gastrointestinal effects. One severe adverse effect, lower abdominal cramping, was considered possibly drug-related.[18]
The most common adverse effects noted were itching (23%), redness (18%), discharge (15%), irregular menstruation (13%), and uterine bleeding (11%). Vaginal candidiasis occurred in 5% of women while using the gel.[19]
In irritation studies, tenofovir 0.3% and 1% gels, adjusted to pH 4 to 5, appear nearly equal to carrier vehicles in irritation scores.[20] |
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Clinical Trials |
| Click here to search ClinicalTrials.gov for trials that use Tenofovir. |
Chemistry |
CAS Name |
| Phosphonic acid, (((1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy)methyl)-[21] |
CAS Number |
| 147127-20-6[22] |
Molecular Formula |
| C9-H14-N5-O4-P[23] |
Elemental Composition |
| C37.64%, H4.91%, N24.38%, O22.28%, P10.78%[24] |
Molecular Weight |
| 287.21[25] |
Melting Point |
| 279 C[26] |
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Physical Description |
| Clear, transparent, viscous gel.[27] |
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Other Names |
PMPA gel[28]
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Further Reading |
PMID/12227991 Tenofovir gel studied. AIDS Patient Care STDS. 2002 Aug;16(8):401-2.
PMID/14754390 D'Cruz OJ, Uckun FM. Clinical development of microbicides for the prevention of HIV infection. Curr Pharm Des. 2004;10(3):315-36.
PMID/16470118 Meyer KH, Maslankowski LA, Gai F, El-Sadr WM, Justman J, Kwiecien A, Masse B, Eshleman SH, Hendrix C, Morrow K, Rooney JF, Soto-Torres L; HPTN 050 Protocol Team. Safety and tolerability of tenofovir vaginal gel in abstinent and sexually active HIV-infected and uninfected women. AIDS 2006 Feb 28;20(4):543-551.
HPTN059: Phase II Expanded Safety and Acceptability Study of the Vaginal Microbicide 1% Tenofovir Gel. Available at: http://www.hptn.org/research_studies/hptn059.asp. Accessed 06/04/08.
Safety and Acceptability of a Vaginal Microbicide. Available at: http://www.clinicaltrials.gov/show/NCT00111943. Accessed 06/04/08.
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Manufacturer Information |
Tenofovir
Gilead Sciences Inc
333 Lakeside Dr
Foster City, CA 94404
(800) 445-3235
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References |
[1] Curr Pharm Des - 2004;10(3):315-36
[2] Treatment Action Group - Microbicides Pipeline - Table 2. Available at: http://aidsinfonyc.org/tag/science/immunePipelineTables.html. Accessed 06/04/08.
[3] AIDS - 2006 Feb 26;20(4): 543-51
[4] Gilead Sciences - Microbicides Pipeline - Table 2. Available at: Investors: News Releases. Gilead Announces Initiation of NIH-sponsored Phase I Trial to Evaluate Tenofovir Topical Gel as Preventive for Vaginal Transmission of HIV [press release], May 21, 2002. Available at: http://www.gilead.com/wt/sec/pr_298978. Accessed 06/04/08.
[5] Infection - 2006 Aug:34(4):234-5
[6] AIDS Read - 2006 Apr;16(4):219-22
[7] AIDS Patient Care STDS - 2006 Dec;20(12):517-22
[8] AIDS - 2006 Feb 26;20(4): 543-51
[9] AIDS - 2006 Feb 26;20(4): 543-51
[10] AIDS - 2006 Feb 26;20(4): 543-51
[11] Gilead Sciences - Investors: News Releases. Gilead Announces Initiation of NIH-sponsored Phase I Trial to Evaluate Tenofovir Topical Gel as Preventive for Vaginal Transmission of HIV [press release], May 21, 2002. Available at: http://www.gilead.com/wt/sec/pr_298978. Accessed 06/04/08.
[12] Gilead Sciences - Investors: News Releases. Gilead Announces Initiation of NIH-sponsored Phase I Trial to Evaluate Tenofovir Topical Gel as Preventive for Vaginal Transmission of HIV [press release], May 21, 2002. Available at: http://www.gilead.com/wt/sec/pr_298978. Accessed 06/04/08.
[13] AIDS - 2006 Feb 26;20(4):543-51
[14] Conf Retroviruses Opportunistic Infect - 13th, 2006. Abstract 569.
[15] Gilead Sciences - Investors: News Releases. Gilead Announces Initiation of NIH-sponsored Phase I Trial to Evaluate Tenofovir Topical Gel as Preventive for Vaginal Transmission of HIV [press release], May 21, 2002. Available at: http://www.gilead.com/wt/sec/pr_298978. Accessed 06/04/08.
[16] AIDS - 2006 Feb 26;20(4):543-51
[17] HPTN - Phase II Expanded Safety and Acceptability Study of the Vaginal Microbicide 1% Tenofovir Gel. Available at: http://www.hptn.org/research_studies/hptn059.asp. Accessed 06/04/08.
[18] AIDS - 2006 Feb 26;20(4): 543-51
[19] AIDS - 2006 Feb 26;20(4): 543-51
[20] AIDS - 2006 Feb 26;20(4): 543-51
[21] ChemIDplus - Available at: http://chem.sis.nlm.nih.gov/chemidplus/chemidlite.jsp. Accessed 06/04/08.
[22] ChemIDplus - Available at: http://chem.sis.nlm.nih.gov/chemidplus/chemlite.jsp. Accessed 06/04/08.
[23] ChemIDplus - Available at: http://chem.sis.nlm.nih.gov/chemidplus/chemidlite.jsp. Accessed 06/04/08.
[24] Merck Index - 2006, p. 1573
[25] Merck Index - 2006, p. 1573
[26] Merck Index - 2006, p. 1573
[27] AIDS - 2006 Feb 26;20(4): 543-51
[28] AIDS - 2006 Feb 26;20(4):543-551
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Updated June 4, 2008
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