Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019163 (hepatitis B)
 38,309 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cidofovir and adefovir are members of a new class of antiviral compounds. They are acyclic phosphonate analogues of deoxynucleoside monophosphates. Both compounds undergo intracellular activation to form diphosphates that are potent inhibitors of viral DNA polymerases. Cidofovir has broad spectrum antiviral activity against herpesviruses, papillomaviruses and poxviruses, whereas adefovir has potent activity against retroviruses and certain DNA viruses, including herpesviruses and hepadnaviruses. Intravenous cidofovir is approved for treatment of cytomegalovirus retinitis in patients with AIDS. Cidofovir and adefovir are dianionic at physiological pH and have low oral bioavailability in animals and humans. After intravenous administration to HIV-infected patients, the pharmacokinetics of both drugs are independent of dose and are consistent with preclinical data. Systemic exposure is proportional to the intravenous dose and both drugs are cleared by the kidney and excreted extensively as unchanged drug in the urine. Intracellular activation of a small fraction (< 10%) of the dose by cellular kinases leads to prolonged antiviral effects that are not easily predicted from conventional pharmacokinetic studies. The observed rate of elimination of cidofovir and adefovir from serum may not reflect the true duration of action of these drugs, since the antiviral effect is dependent on concentrations of the active phosphorylated metabolites that are present within cells. For both drugs, > 90% of an intravenous dose is recovered unchanged in the urine over 24 hours. Metabolism does not contribute significantly to the total clearance of either drug. Concomitant oral probenecid decreases both the renal clearance of cidofovir and the incidence of nephrotoxicity, presumably by blocking its active tubular secretion. This is the basis of the clinical use of concomitant probenecid as a nephroprotectant during cidofovir therapy. Subcutaneous administration produces exposure equivalent to that following intravenous administration. Drug interaction studies with cidofovir are ongoing, but there is no evidence of an interaction between zidovudine and either cidofovir or adefovir. Clearance of cidofovir in patients with renal impairment showed a linear relationship to creatinine clearance. The low oral bioavailability of adefovir has led to the development of an oral prodrug, adefovir dipivoxil, currently in development for the treatment of HIV and hepatitis B infections.
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PMID:Clinical pharmacokinetics of the antiviral nucleotide analogues cidofovir and adefovir. 1009 59

The incidence of cytomegalovirus (CMV) retinitis in AIDS has declined significantly due to the use of highly active antiretroviral therapy (HAART). However, patients with HIV, especially those failing HAART, may still suffer with CMV retinitis, which can lead to significant loss of vision and blindness. Ganciclovir has traditionally been considered the recommended treatment for CMV retinitis; however, due to side effects and the possibility of developing viral resistance, other agents may be preferred in certain situations. Foscarnet, which has similar efficacy to ganciclovir but a different side effect profile, is more difficult to administer and is less well-tolerated. Intravenous cidofovir, which may be more effective than either iv. ganciclovir or foscarnet, can also be used as a first line agent; however, it is associated with toxicity (renal and ocular) and thus needs careful use. Local therapy for CMV retinitis has been a significant advance. The intraocular ganciclovir implant has the highest efficacy of the approved agents and is well-tolerated. Fomivirsen, an oligonucleotide injected intravitreally, is a newly approved agent which offers alternative treatment. Intravitreal ganciclovir or foscarnet, although not approved, have been used successfully in some patients especially those with recurrent or refractory disease. The development of new anti-CMV agents has been stalled by the decreased incidence of the disease. Valganciclovir, a prodrug of ganciclovir, offers excellent oral bioavailability and is the closest to approval of all the new anti-CMV drugs. High ganciclovir blood levels are achieved without the complications associated with the requirement for long-term iv. access. The monoclonal antibody (mAb) MSL-109, did not offer a significant advantage when added to traditional anti-CMV therapy. Development plans of other agents such as cyclic HPMPC and lobucavir have been put on hold by their respective manufacturers. Adefovir is a nucleotide analogue that possesses anti-CMV activity, but is currently only being pursued for the treatment of hepatitis B virus. Other compounds possessing significant anti-CMV activity, including BAY 38-4766 and GW1263W94 are still in the early stages of development.
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PMID:Therapeutic developments in cytomegalovirus retinitis. 1106 Jun 72

New approaches to treating opportunistic infections in people with HIV are discussed. The approaches include the following areas: fungal infections, hepatitis B, and CMV retinitis. Study highlights of itraconazole for preventing some fungal infections and intravenous amphotericin B with IV liposomal amphotericin B for treating cryptococcal meningitis are provided, as is information on adefovir dipivoxil for hepatitis B, and cidofovir (Vistide) for treating cytomegalovirus infection. Highlights include drug dosages used and side effects associated with treatment. Guidelines for the proper use of the intravenous (IV) formulation of cidofovir, following reports of a few cases of one or two doses of IV cidofovir leading to kidney damage and possibly contributing to death, are also included.
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PMID:Opportunistic infections update. 1136 66

Open clinical trials for treatments of HIV infection are discussed, including marijuana and dronabinol, zintevir, indinavir, abacavir, and MKC-442. A study is open in San Francisco to evaluate the use of SU5416 for Kaposi's sarcoma. Studies for the treatment and prevention of opportunistic infections, including hepatitis B, CMV retinitis, and candidiasis are listed. Details and contact information for each study are provided.
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PMID:Open clinical trials for HIV/AIDS treatments. 1136 64

The acyclic nucleoside phosphonates HPMPC (cidofovir), PMEA (adefovir), and PMPA (tenofovir) have proved to be effective in vitro (cell culture systems) and in vivo (animal models and clinical studies) against a wide variety of DNA virus and retrovirus infections: cidofovir against herpesvirus (herpes simplex virus types 1 and 2 varicella-zoster virus, cytomegalovirus [CMV], Epstein-Barr virus, and human herpesviruses 6, 7, and 8), polyomavirus, papillomavirus, adenovirus, and poxvirus (variola virus, cowpox virus, vaccinia virus, molluscum contagiosum virus, and orf virus) infections; adefovir against herpesvirus, hepadnavirus (human hepatitis B virus), and retrovirus (human immunodeficiency virus types 1 [HIV-1] and 2 [HIV-2], simian immunodeficiency virus, and feline immunodeficiency virus) infections; and tenofovir against both hepadnavirus and retrovirus infections. Cidofovir (Vistide) has been officially approved for the treatment of CMV retinitis in AIDS patients, tenofovir disoproxil fumarate (Viread) has been approved for the treatment of HIV infections (i.e., AIDS), and adefovir dipivoxil (Hepsera) has been approved for the treatment of chronic hepatitis B. Nephrotoxicity is the dose-limiting side effect for cidofovir (Vistide) when used intravenously (5 mg/kg); no toxic side effects have been described for adefovir dipivoxil and tenofovir disoproxil fumarate, at the approved doses (Hepsera at 10 mg orally daily and Viread at 300 mg orally daily).
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PMID:Clinical potential of the acyclic nucleoside phosphonates cidofovir, adefovir, and tenofovir in treatment of DNA virus and retrovirus infections. 1455 87

The acyclic nucleoside phosphonates [HPMPC: cidofovir, Vistide; PMEA: adefovir dipivoxil, Hepsera; and PMPA: tenofovir, Viread] have proven to be effective in vitro (cell culture systems) and in vivo (animal models and clinical studies) against a wide variety of DNA virus and retrovirus infections, for example, cidofovir against herpesvirus [herpes simplex virus type 1 and 2, varicella-zoster virus, cytomegalovirus, Epstein-Barr virus, human herpesvirus type 6, 7 and 8), polyoma-, papilloma-, adeno- and poxvirus (variola virus, cowpox virus, vaccinia virus, molluscum contagiosum virus and orf) infections; adefovir against herpesvirus, hepadnavirus [human hepatitis B virus] and retrovirus [HIV type-1 and 2, simian immunodeficiency virus and feline immunodeficiency virus] infections; and tenofovir against both hepadna- and retrovirus infections. Cidofovir has been officially approved for the treatment of cytomegalovirus retinitis in AIDS patients, tenofovir disoproxil fumarate (Viread) for the treatment of HIV infections (i.e., AIDS) and adefovir dipivoxil for the treatment of chronic hepatitis B.
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PMID:Potential of acyclic nucleoside phosphonates in the treatment of DNA virus and retrovirus infections. 1548

The use of highly active antiretroviral therapy (HAART) in the management of human immunodeficiency virus (HIV) infection has resulted paradoxically in the worsening of clinical symptoms of previously subclinical infections, such as herpes zoster (HZ), herpes simplex, angular cheilitis, warts, tuberculosis, hepatitis B and C, cytomegalovirus retinitis, and others, as a result of substantial reconstitution of the host's immune responses. This phenomenon is referred to as immune reconstitution inflammatory syndrome (IRIS). It may affect up to 32% of HIV-seropositive subjects within a wide range of time after the initiation of HAART, but mainly after 8-12 weeks. Mucocutaneous HZ accounts for 7%-12% of the diseases associated with HIV infection that become worse again when the subject's immunity improves from the administration of HAART. It usually occurs after 4 weeks from the initiation of HAART, and under these circumstances the clinical symptoms and natural course of mucocutaneous HZ are similar to those in HIV-seropositive subjects who do not manifest IRIS.
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PMID:Herpes zoster infection as an immune reconstitution inflammatory syndrome in HIV-seropositive subjects: a review. 1760 57

In this paper, we review sexually transmitted diseases (STD) involving the eye. Recently conjunctivitis due to Chlamydia trachomatis in children and adults is increasing, and that of Neisseria gonorrhoeae resistant to multiple antibiotics has attracted special attention in our country. Syphilis has many ocular manifestations such as keratitis, iridocyclitis, retinochorioiditis, and neuritis, etc. Ocular complications related to HIV infection, including HIV retinopathy, cytomegalovirus retinitis, zoster ophthalmics, and Kaposi s sarcoma in conjunctiva are increasing in Japan. Phthirus pubis infection of the eye lid, and human T-cell lymphotropic virus type 1 (HTLV-1)-associated uveitis are occasionally reported. Furthermore conjunctival tumor associated with human papilloma virus (HPV) infection, acute retinal necrosis(ARN) due to herpes simplex virus type 2 (HSV-2), as well as hepatitis B virus (HVB) and hepatitis C virus (HVC) retinopathy are also mentioned in this review.
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PMID:[STD in the eye]. 1917 59