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Antimicrobial Agents and Chemotherapy Feb 1985Oral acyclovir was evaluated for its effectiveness in treating guinea pigs with primary herpes simplex virus type 2 infections. Guinea pigs inoculated intravaginally...
Oral acyclovir was evaluated for its effectiveness in treating guinea pigs with primary herpes simplex virus type 2 infections. Guinea pigs inoculated intravaginally with acyclovir-susceptible strains (for which 50% inhibitory concentrations of acyclovir in cell culture were found to be in the range of 0.15 to 1.2 micrograms/ml) and treated with 5.0 mg of acyclovir per ml in the drinking water beginning 48 h postinfection showed significant reductions in lesion severity. This dosage produced serum acyclovir levels of 1.3 micrograms/ml. Lower concentrations of oral acyclovir (less than or equal to 2.5 mg/ml in the drinking water), which produced serum acyclovir levels of less than 1.0 microgram/ml, were less consistently effective against these same virus strains. When an acyclovir-resistant isolate (for which the 50% inhibitory concentration of acyclovir in cell culture was found to be 8.5 micrograms/ml) was used to initiate infection, treatment with 5 or 10 mg/ml (yielding serum levels of 1.3 and 3.5 micrograms/ml) in the drinking water had only minimal clinical benefit. However, the degree of response was difficult to determine because of the attenuated disease produced by the acyclovir-resistant virus. In vitro virus sensitivity may be predictive of the serum drug levels that need to be obtained to produce a successful response to therapy.
Topics: Acyclovir; Administration, Oral; Animals; Cells, Cultured; Female; Guinea Pigs; Herpes Genitalis; Male; Microbial Sensitivity Tests; Simplexvirus; Vagina
PubMed: 2984984
DOI: 10.1128/AAC.27.2.167 -
Journal of the American Academy of... Jan 1988A screening program for antiviral drugs begun at Burroughs Wellcome in the 1960s resulted in the discovery of acyclovir in 1974. Preclinical investigation brought the...
A screening program for antiviral drugs begun at Burroughs Wellcome in the 1960s resulted in the discovery of acyclovir in 1974. Preclinical investigation brought the drug to clinical trials in 1977 and the first form of the drug (topical) was available to physicians in 1982. Activity of acyclovir is greatest against herpes 1 and herpes 2, less against varicella zoster, still less against Epstein-Barr, and very little against cytomegalovirus. Acyclovir is an antiviral agent only after it is phosphorylated in infected cells by a viral-induced thymidine kinase. Acyclovir monophosphate is phosphorylated to diphosphate and triphosphate forms by cellular enzymes in the infected host cell where the drug is concentrated. Acyclovir triphosphate inactivates viral deoxyribonucleic acid polymerase. Acyclovir incorporation into the growing viral deoxyribonucleic acid chain causes its termination. The antiviral process has relatively little effect on normal, uninfected cells. An important toxic effect of acyclovir is its potential to cause obstructive nephropathy. The drug is excreted primarily by the kidney, which may require smaller doses in patients with decreased kidney function. Oral dosages of acyclovir as recommended for herpes simplex are probably not adequate for varicella zoster infections.
Topics: Acyclovir; Animals; Cytomegalovirus; Herpesvirus 3, Human; Herpesvirus 4, Human; History, 20th Century; Humans; Simplexvirus
PubMed: 2828440
DOI: 10.1016/s0190-9622(88)70022-5 -
Clinical & Experimental Ophthalmology Apr 2010Herpes simplex virus (HSV) keratitis is a common cause of ocular morbidity. Resistance to aciclovir is probably under recognized. We describe three cases of... (Review)
Review
Herpes simplex virus (HSV) keratitis is a common cause of ocular morbidity. Resistance to aciclovir is probably under recognized. We describe three cases of aciclovir-resistant herpes simplex virus keratitis treated with systemic foscarnet and present a review of the pharmacological options available to manage this condition.
Topics: Acyclovir; Administration, Oral; Administration, Topical; Aged, 80 and over; Antiviral Agents; Blindness; Drug Resistance, Viral; Humans; Keratitis, Herpetic; Male; Middle Aged; Treatment Outcome
PubMed: 20447128
DOI: 10.1111/j.1442-9071.2010.02209.x -
American Journal of Obstetrics and... Mar 1988Acyclovir concentration was measured by radioimmunoassay in the serum and milk of a lactating woman who was treated with oral acyclovir for herpes zoster. Daily serum...
Acyclovir concentration was measured by radioimmunoassay in the serum and milk of a lactating woman who was treated with oral acyclovir for herpes zoster. Daily serum and milk samples showing milk concentrations that averaged being 3.24-fold higher than serum levels suggest a low infant dose. The elimination phase demonstrated a half-life of 2.8 hours in milk.
Topics: Acyclovir; Adult; Female; Half-Life; Humans; Milk, Human; Radioimmunoassay
PubMed: 3348321
DOI: 10.1016/0002-9378(88)90033-6 -
Zeitschrift Fur Naturforschung. C,... 2010New acyclovir esters with peptidomimetics were synthesized and evaluated in vitro for their antiviral activity against the replication of Herpes simplex virus type 1...
New acyclovir esters with peptidomimetics were synthesized and evaluated in vitro for their antiviral activity against the replication of Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2). The influence of peptidomimetics containing oxazole and thiazolyl-thiazole moieties on the antiviral activity is also reported. The esters were synthesized using the coupling reagents N-ethyl-N'-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) and N,N-dimethyl-4-aminopyridine (DMAP) as a catalyst.
Topics: Acyclovir; Antiviral Agents; Carbodiimides; Esters; Herpesvirus 1, Human; Pyridines; Virus Replication
PubMed: 20355317
DOI: 10.1515/znc-2010-1-205 -
Artificial Cells, Nanomedicine, and... Mar 2018The present study was aimed to develop and evaluate a microemulsion-based dermal drug delivery of an antiviral agent, acyclovir. A water-in-oil microemulsion was...
The present study was aimed to develop and evaluate a microemulsion-based dermal drug delivery of an antiviral agent, acyclovir. A water-in-oil microemulsion was prepared using isopropyl myristate, Tween 20, Span 20, water and dimethylsulphoxide. It was characterized for drug content, stability, globule size, pH, viscosity and ex vivo permeation through mice skin. In vivo antiviral efficacy of optimized formulation was assessed in female Balb/c mice against herpes simplex virus-I (HSV-I)-induced infection. It was observed that optimized formulation when applied 24-h post-infection could completely inhibit the development of cutaneous herpetic lesions vis-à-vis marketed cream.
Topics: Acyclovir; Animals; Disease Models, Animal; Drug Carriers; Drug Compounding; Emulsions; Female; Herpes Simplex; Herpesvirus 1, Human; Mice; Mice, Inbred BALB C; Oils; Permeability; Skin; Solubility; Thermodynamics; Water
PubMed: 28403666
DOI: 10.1080/21691401.2017.1313262 -
The Journal of Antimicrobial... Jun 2004While active against Herpesviridae, oral aciclovir is limited by low and inconsistent bioavailability. Modification of aciclovir by valine esterification, producing... (Review)
Review
While active against Herpesviridae, oral aciclovir is limited by low and inconsistent bioavailability. Modification of aciclovir by valine esterification, producing valaciclovir, results in significant increases in systemic aciclovir plasma levels. The exact mechanism of increased absorption with valaciclovir is not fully determined but probably involves intestinal dipeptide transporters, followed by rapid ester hydrolysis in the small intestine and liver. The enhanced pharmacokinetics of valaciclovir have translated into improvements in clinical efficacy and patient convenience.
Topics: Acyclovir; Animals; Antiviral Agents; Biotransformation; Carrier Proteins; Humans; Hydrolysis; Peptide Transporter 1; Symporters; Valacyclovir; Valine
PubMed: 15140857
DOI: 10.1093/jac/dkh244 -
Nederlands Tijdschrift Voor Geneeskunde Sep 1996
Topics: Acyclovir; Antiviral Agents; Herpes Labialis; Humans; Nonprescription Drugs; Ointments
PubMed: 8927151
DOI: No ID Found -
Nederlands Tijdschrift Voor Geneeskunde Sep 1996
Topics: Acyclovir; Antiviral Agents; Drug Resistance, Microbial; Humans; Virus Diseases
PubMed: 8927150
DOI: No ID Found -
Nederlands Tijdschrift Voor Geneeskunde Jul 1996
Topics: Acyclovir; Drug Resistance, Microbial; Humans; Nonprescription Drugs; Simplexvirus
PubMed: 8766686
DOI: No ID Found