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gmx.de

Forty-three consecutive cases of acute aseptic meningitis (AAM) presenting within a 24-months period were retrospectively analysed with respect to clinical symptomatology, cerebrospinal fluid (CSF) findings, clinical course, treatment and outcome. Nineteen of the 43 AAM cases (44%) were caused by enterovirus, one by HIV (2%), two by Varicella zoster virus (5%), three due to herpes simplex virus I (7%), two due to herpes simplex virus II (5%), one due to Central European encephalitis virus (2%), and in 15 patients (35%) the aetiology of AAM remained unknown. Headache (100%) and fever (93%) were the presenting symptoms in the majority of cases. Signs of preceding infection were predominantly gastrointestinal in the enterovirus subgroup, but were inconsistently observed in the other subgroups. CSF findings at the first lumbar tap on admission generally revealed lymphomonocytic pleocytosis of less than 500 cells per micro l, mild to moderately elevated protein and normal lactate and glucose levels. Initial therapy consisted of an empirical antiviral and antibiotic regimen until a serological diagnosis was available. Acyclovir, effective only in herpes family viruses, was initially administered to all AAM cases. Effective therapy for other viral pathogens are not broadly available and treating AAM of unknown aetiology imposes a particular problem. The average hospitalization time ranged from 16 to 31 days. Patients were either discharged home (72%) or transferred to a rehabilitation centre (28%). The outcome was good (40%) to fair (51%) in the majority of cases.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12752401&dopt=Abstract

Pharm Dev Technol. 2003;8(2):199-208.
Buccal delivery of acyclovir from films based on chitosan and polyacrylic acid.

Rossi S, Sandri G, Ferrari F, Bonferoni MC, Caramella C.

Department of Pharmaceutical Chemistry, University of Pavia, Pavia, Italy.

The aim of the present work was to investigate the possibility of achieving buccal delivery of a problematic drug, acyclovir, from films based on chitosan hydrochloride (HCS) and polyacrylic acid sodium salt (PAA). At first, the ionic interaction between HCS and PAA in distilled water was investigated by means of rheological and turbidimetric analysis. Films containing 1 mg/cm2 of acyclovir and based on pure HCS and on HCS and PAA mixed in different ratios were prepared by casting technique. The films were subjected to hydration, rheological, mucoadhesion, drug release, "wash away," and permeation/penetration measurements. A commercial cream containing acyclovir and an aqueousacyclovir suspension were used as references. The addition of PAA to HCS produced a decrease in film hydration. Films based on HCS/PAA weight ratio close to interaction productstoichiometry were characterized by higher rigidity and better "wash away" properties with respect to the other films and the reference formulation. The worst mucoadhesive properties were shown by films based on mixing ratios close to interaction product stoichiometry. The addition of PAA to HCS produced a lowering in drug release profile. All the films examined promoted the permeation of acyclovir across porcine cheek epithelium when compared with acyclovir suspension and the commercial cream. The penetration enhancement properties were affected by the mixing ratio of the two polymers. The film based on 1/1.3 HCS/PAA weight ratio, besides possessing the best resilience properties on the mucosa, was also characterized by the highest permeation profile and, therefore, represents a promising formulation for buccal delivery of acyclovir.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12760570&dopt=Abstract

lav.boehringer-ingelheim.com

This study investigated the oral bioavailability and efficacy of BILS 45 BS, a selective herpes simplex virus (HSV) helicase-primase inhibitor, against acyclovir (ACV)-resistant (ACV(r)) infections mediated by the HSV type 1 (HSV-1) dlsptk and PAA(r)5 mutant strains. In vitro, the compound was more potent than ACV against wild-type clinical and laboratory HSV-1 strains and ACV(r) HSV isolates, as determined by a standard plaque reduction assay, with a mean 50% effective concentration of about 0.15 microM. The oral bioavailability of BILS 45 BS in hairless mice was 49%, with a peak concentration in plasma of 31.5 microM after administration of a single dose of 25 mg/kg. Following cutaneous infection of nude mice, both the HSV-1 dlsptk and PAA(r)5 mutant strains induced significant, reproducible, and persistent cutaneous lesions that lasted for more than 2 weeks. Oral treatment with ACV (100 or 125 mg/kg/day, three times a day by gavage) did not affect either mutant-induced infection. In contrast, BILS 45 BS at an oral dose of 100 mg/kg/day almost completely abolished cutaneous lesions mediated by both ACV(r) HSV-1 mutants. The 50% effective doses of BILS 45 BS were 56.7 and 61 mg/kg/day against dlsptk- and PAA(r)5-induced infections, respectively. Taken together, our results demonstrate very effective oral therapy of experimental ACV(r) HSV-1 infections in nude mice and support the potential use of HSV helicase-primase inhibitors for the treatment of nucleoside-resistant HSV disease in humans.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12760851&dopt=Abstract

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