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The American Journal of Medicine Feb 1992Foscarnet exerts its antiviral effects via reversible inhibition of viral polymerases. Pharmacodynamic data indicate that herpesvirus and human immunodeficiency virus... (Review)
Review
Foscarnet exerts its antiviral effects via reversible inhibition of viral polymerases. Pharmacodynamic data indicate that herpesvirus and human immunodeficiency virus replication is inhibited by therapeutically achievable concentrations of foscarnet; however, the concentrations of foscarnet required for such inhibition have been found to vary widely. Pharmacokinetic data indicate that foscarnet is eliminated via the renal route, undergoes negligible metabolism, and appears to be distributed widely from the circulation. However, the available data indicate that the pharmacokinetics of the drug varies among patients and within the individual patient, particularly with regard to plasma drug levels; furthermore, such factors as the intracellular kinetics of the drug have yet to be well characterized. It is thus difficult to formulate optimal dosing regimens on the basis of what is known of foscarnet pharmacodynamics and pharmacokinetics. Nevertheless, dosages that produce clear-cut therapeutic benefits without unacceptable toxicity have been identified in clinical trials of foscarnet in acquired immunodeficiency syndrome (AIDS) patients with cytomegalovirus (CMV) retinitis.
Topics: Antiviral Agents; Foscarnet; HIV; Humans; Nucleic Acid Synthesis Inhibitors; Phosphonoacetic Acid; Reverse Transcriptase Inhibitors
PubMed: 1371039
DOI: 10.1016/0002-9343(92)90330-e -
The American Journal of Medicine Feb 1992Foscarnet is a pyrophosphate analogue with activity against herpesviruses, human immunodeficiency virus (HIV), and other RNA and DNA viruses. Foscarnet and its analogues... (Review)
Review
Foscarnet is a pyrophosphate analogue with activity against herpesviruses, human immunodeficiency virus (HIV), and other RNA and DNA viruses. Foscarnet and its analogues achieve their antiviral effects via inhibition of viral polymerases, with such inhibition not being dependent on activation or phosphorylation of the compounds by viral or cellular proteins. Current evidence indicates that foscarnet interferes with exchange of pyrophosphate from deoxynucleoside triphosphate during viral replication by binding to a site on the herpesvirus DNA polymerase or HIV reverse transcriptase. Reviewed herein are basic findings regarding the mechanism of action and antiviral activity of foscarnet and the related compound phosphonoacetic acid (PAA), as well as findings regarding potential mechanisms of viral resistance and interactions with other antiviral agents.
Topics: Antiviral Agents; DNA-Directed RNA Polymerases; Drug Interactions; Drug Resistance, Microbial; Foscarnet; Ganciclovir; HIV; HIV Reverse Transcriptase; Herpesviridae; Humans; Nucleic Acid Synthesis Inhibitors; Phosphonoacetic Acid; Reverse Transcriptase Inhibitors; Simplexvirus
PubMed: 1371038
DOI: 10.1016/0002-9343(92)90329-a -
Journal of Acquired Immune Deficiency... 1992The primary dose-limiting adverse effects associated with foscarnet treatment of cytomegalovirus retinitis in patients with AIDS are renal impairment and ionized... (Review)
Review
The primary dose-limiting adverse effects associated with foscarnet treatment of cytomegalovirus retinitis in patients with AIDS are renal impairment and ionized hypocalcemia. Dose-limiting renal impairment, consisting of significant alterations in serum creatinine levels or creatinine clearance or acute renal failure, has been observed in 10-20% of AIDS patients receiving foscarnet via intermittent i.v. infusion. Nephrotoxicity can be minimized by adjusting dosage according to creatinine clearance and by ensuring that adequate hydration is provided throughout foscarnet therapy. Transient decreases in serum or plasma ionized calcium levels appear to occur in all patients during foscarnet infusion, with these decreases being observed in the absence of changes in total calcium levels. Hypocalcemia produces mild symptoms in some patients and may play a role in unexplained cases of arrhythmia or seizure. Careful attention should be given to levels of total calcium and other minerals during foscarnet treatment, and the occurrence of symptomatic hypocalcemia should prompt evaluation of ionized calcium concentrations and foscarnet dose reduction. Another potentially treatment-limiting effect attributed to foscarnet is penile ulceration, which appears to result from exposure of the glans penis to unchanged foscarnet in the urine.
Topics: Antiviral Agents; Foscarnet; Humans; Phosphonoacetic Acid
PubMed: 1534839
DOI: No ID Found -
Current Opinion in Dentistry Aug 1991Rapid progress is being made in the development of antiviral therapy. This review restricts its focus to antivirals that may be used by dental practitioners, principally... (Review)
Review
Rapid progress is being made in the development of antiviral therapy. This review restricts its focus to antivirals that may be used by dental practitioners, principally those agents active in herpesvirus infections.
Topics: Acyclovir; Antiviral Agents; Dental Care; Drug Combinations; Drug Resistance, Microbial; Foscarnet; Herpesviridae Infections; Humans; Immunocompromised Host; Interferons; Nucleosides; Phosphonoacetic Acid; Viral Vaccines
PubMed: 1724924
DOI: No ID Found -
The British Journal of Ophthalmology Aug 1977In the rabbit 5% phosphonoacetic acid ointment suppressed herpetic keratitis as well as 0-5% idoxuridine ointment. After 5 days of treatment quantitative virus titres... (Comparative Study)
Comparative Study
In the rabbit 5% phosphonoacetic acid ointment suppressed herpetic keratitis as well as 0-5% idoxuridine ointment. After 5 days of treatment quantitative virus titres showed that phosphonoacetic acid was superior to idoxuridine in the inhibition of herpes virus replication. Phosphonoacetic acid was found to be nontoxic to the eye in both clinical and histopathological studies. Recent reports suggest that the mechanism of action of phosphonoacetic acid appears to be the blocking of the virus DNA polymerase, which is essential for the synthesis of herpes virus DNA.
Topics: Animals; Idoxuridine; Keratitis, Dendritic; Organophosphorus Compounds; Phosphonoacetic Acid; Rabbits; Simplexvirus
PubMed: 199232
DOI: 10.1136/bjo.61.8.506 -
Cancer Practice 1999
Review
Topics: Antineoplastic Combined Chemotherapy Protocols; Aspartic Acid; Colorectal Neoplasms; Drug Interactions; Fluorouracil; Humans; Intestinal Absorption; Metabolic Clearance Rate; Phosphonoacetic Acid; Treatment Outcome
PubMed: 10687588
DOI: 10.1046/j.1523-5394.1999.74011.x -
Pharmacotherapy 1992The diseases caused by cytomegalovirus (CMV) may threaten the life or sight of immunocompromised individuals such as patients undergoing transplantation and those with... (Review)
Review
The diseases caused by cytomegalovirus (CMV) may threaten the life or sight of immunocompromised individuals such as patients undergoing transplantation and those with the acquired immunodeficiency syndrome. The management of CMV disease can be difficult. The antiviral agents ganciclovir and foscarnet are effective against CMV retinitis and gastrointestinal diseases, although dose-limiting adverse effects and the need for long-term maintenance therapy may hinder their use in many patients. When used to treat CMV pneumonitis in bone marrow transplant recipients, ganciclovir alone is not as effective as when it is combined with immune globulin. Since CMV disease can be fatal, several protocols have been developed for the transplant patient population, including administration of acyclovir, ganciclovir, screened blood products, and immune globulins.
Topics: Acquired Immunodeficiency Syndrome; Antiviral Agents; Cytomegalovirus Infections; Foscarnet; Ganciclovir; Gastroenteritis; Humans; Immunocompromised Host; Immunoglobulins, Intravenous; Phosphonoacetic Acid; Pneumonia, Viral; Retinitis
PubMed: 1325636
DOI: No ID Found -
Dental Materials Journal Feb 2012This paper reviews the developments of dithiooctanoate monomers and acidic adhesive monomers, and their roles in multi-purpose primers and adhesives in promoting... (Review)
Review
This paper reviews the developments of dithiooctanoate monomers and acidic adhesive monomers, and their roles in multi-purpose primers and adhesives in promoting adhesion to multiple substrate materials. Novel dithiooctanoate monomers exhibited excellent bonding to precious metals and alloys when compared against conventional sulfur-containing monomers. Newly developed phosphonic acid monomers, endowed with a water-soluble nature, enabled sufficient demineralization of dental hard tissues and thus improved bonding to both ground enamel and dentin. The optimal combination for bonding to dental hard tissues and precious and non-precious metals and alloys was 5.0 wt% 10-methacryloyloxydecyl 6,8-dithiooctanoate (10-MDDT) and 1.0 wt% 6-methacryloyloxyhexyl phosphonoacetate (6-MHPA). For bonding to dental porcelain, alumina, zirconia, and gold (Au) alloy, a ternary combination of silane coupling agent, acidic adhesive monomers, and dithiooctanoate monomers seemed promising. The latest development was a single-bottle, multi-purpose, self-etching adhesive which contained only acidic adhesive monomers and dithiooctanoate monomers but which produced strong adhesion to ground enamel and dentin, sandblasted zirconia, and Au alloy.
Topics: Caprylates; Dental Alloys; Dental Bonding; Dental Cements; Dental Enamel; Dentin; Humans; Methacrylates; Organophosphonates; Phosphonoacetic Acid; Phosphorous Acids; Sulfur Compounds
PubMed: 22277601
DOI: 10.4012/dmj.2011-139 -
Antiviral Chemistry & Chemotherapy Jul 2003Continuing our investigations on inhibitors of ribonucleotide reductase (RNR), the crucial enzyme that catalyses the reduction of ribonucleotides to...
Design and synthesis of phosphonoacetic acid (PPA) ester and amide bioisosters of ribofuranosylnucleoside diphosphates as potential ribonucleotide reductase inhibitors and evaluation of their enzyme inhibitory, cytostatic and antiviral activity.
Continuing our investigations on inhibitors of ribonucleotide reductase (RNR), the crucial enzyme that catalyses the reduction of ribonucleotides to deoxyribonucleotides, we have now prepared and evaluated 5'-phosphonoacetic acid, amide and ester analogues of adenosine, uridine and cytidine with the aim to verify both substrate specificity and contribution to biological activity of diphosphate mimic moieties. A molecular modelling study has been conducted on the RNR R1 subunit, in order to verify the possible interaction of the proposed bioisosteric moieties. The study compounds were finally tested on the recombinant murine RNR showing a degree of inhibition that ranged from 350 microM for the UDP analogue 5'-deoxy-5'-N-(phosphon-acetyl)uridine sodium salt (amide) to 600 microM for the CDP analogue 5'-O-[(diethyl-phosphon)acetyl]cytidine (ester). None of the tested compounds displayed noteworthy cytostatic activity at 100-500 microM concentrations, whereas ADP analogue 5'-N-[(diethyl-phosphon) acetyl]adenosine (amide) and 5'-deoxy-5'-N-(phosphon-acetyl)adenosine sodium salt (amide) showed a moderate inhibitory activity (EC50: 48 microM) against HSV-2 and a modest inhibitory activity (EC50: 110 microM) against HIV-1, respectively.
Topics: Amides; Animals; Antiviral Agents; Binding Sites; Cell Line; Cell Line, Tumor; Drug Design; Enzyme Inhibitors; Esters; HIV-1; Inhibitory Concentration 50; Mice; Models, Molecular; Molecular Conformation; Molecular Structure; Nucleosides; Phosphonoacetic Acid; Ribonucleotide Reductases
PubMed: 14582847
DOI: 10.1177/095632020301400403 -
Archives of Virology 1981Both myxoma and fibroma viruses were found to be sensitive in vitro to the effects of phosphonoacetic acid. Detectable myxoma virus replication was inhibited at a drug...
Both myxoma and fibroma viruses were found to be sensitive in vitro to the effects of phosphonoacetic acid. Detectable myxoma virus replication was inhibited at a drug concentration of 100 micrograms/ml. Fibroma virus replication was inhibited at a concentration of 500 micrograms/ml. Because of this difference in sensitivity, myxoma virus was used to infect rabbits to test that efficacy of phosphonoacetic acid in the treatment of a systemic viral disease. Rabbits were given 400 mg kg-1 day-1 of phosphonoacetic acid subcutaneously in two injections. Phosphonoacetic acid-treated animals showed a reduction in the severity of disease. Neither serum viral antigen nor infectious virus could be detected. In phosphate buffered saline-treated animals both serum viral antigen and infectious virus were found. All animals treated with phosphate buffered saline died of myxomatosis.
Topics: Animals; Antibodies, Viral; Antiviral Agents; Myxoma virus; Myxomatosis, Infectious; Organophosphorus Compounds; Phosphonoacetic Acid; Rabbits; Viral Plaque Assay; Virus Replication
PubMed: 7332492
DOI: 10.1007/BF01315009