摘要:

The pharmacokinetic disposition of 5-fluorocytosine (5-FC) was studied in 7 patients with acute renal failure undergoing continuous hemofiltration (CH). CH was performed with a high-flux membrane and the average filtration rate (FR) was 16.3 ml/min. Following an intravenous loading dose of 2,500 mg, 5-FC concentrations were measured in plasma and ultrafiltrate. The half-lives of 5-FC were markedly prolonged in all patients, ranging from 15.9 to 37.2 h and longer half-lives corresponded to lower FR. The clearance of 5-FC averaged 97.5% of the FR. Within 48 h, 29–35% of the administered dose was recovered in the ultrafiltrate of 3 patients. The volume of distribution ranged from 0.772 to 0.982 l/kg. We found a linear relationship between the elimination rate constant and the FR, and based on these data, a dosage schedule is proposed regarding the use of 5-FC in patients treated with C

ISSN:0009-3157    

DOI:10.1159/000238478

出版商:S. Karger AG    

年代:1987

数据来源: Karger

摘要:

Sagamicin is an aminoglycosidic antibiotic produced by Micromonospora sagamiensis, chemically related with gentamicin. Single- and multiple-dose pharmacokinetics have been investigated in patients affected by bronchopulmonary infections treated with 60 mg sagamicin i.m. every 12 h. The two concentration-time curves for sputum and serum are parallel; while there is no evidence of accumulation in the serum at the 7th day of treatment, sagamicin concentrations in the sputum are significantly higher on the 7th day, and this is also confirmed by a remarkable difference between the two AUC values. The good penetration power of sagamicin into sputum makes this antibiotic useful for the treatment of infections of the respiratory tract.

ISSN:0009-3157    

DOI:10.1159/000238479

出版商:S. Karger AG    

年代:1987

数据来源: Karger

摘要:

Twenty-four patients, hospitalized in order to undergo radical gynaecological surgery, were orally administered cefatrizine in a single dose of 1 g at different times before surgery. The tissue levels determined in the organs considered (uterus, ovary, tubae, vagina) proved that cefatrizine possesses good absorption in the genital tract, reaching concentrations near to the MICs of most gram-negative and gram-positive sensitive bacteria lasting even 12 h after administration.

ISSN:0009-3157    

DOI:10.1159/000238480

出版商:S. Karger AG    

年代:1987

数据来源: Karger

摘要:

The inducing capacity of mecillinam in combination with ampicillin or ceftazidime was compared with that of the compounds administered separately and related to the inducing capacity of cefoxitin (1 and 10 μg/ml)for the chromosomal β-lactamases from Enterobacter cloacae, Serratia marcescens, Citrobacter freundii, indole-positive Proteus, and Acinetobacter strains. In the majority of the strains all compounds tested alone or in combination showed a lower inducing capacity than cefoxitin at both concentrations (less than twofold); in a few strains a moderate inducing capacity was observed. In general, the inducing capacity of cefoxitin 10 μg/ml was similar to that of 1 μg/ml. Only in two E. cloacae, two S. marcescens and two indole-positive Proteus strains did 10 μg/ml cefoxitin show a distinctly higher inducing capacity. The variation in inducing capacity within one species and between the species was remark

ISSN:0009-3157    

DOI:10.1159/000238481

出版商:S. Karger AG    

年代:1987

数据来源: Karger

摘要:

The antimicrobial activity of carumonam (Ro 17–2301) was compared with that of 20 antibiotics against 338 clinical isolates. Carumonam did not possess activity against gram-positive cocci, MIC90 of carumonam were ≤0.5 mg/l for Enterobacteriaceae, except for Citrobacter (≤8 mg/l) and ≤32 mg/l for nonfermenters. It was slightly more active than aztreonam against gentamicin-resistant bacilli (MIC90 ≤64 vs ≥256). Combinations of carumonam with antibiotics with activity against gram-positive microorganisms were

ISSN:0009-3157    

DOI:10.1159/000238482

出版商:S. Karger AG    

年代:1987

数据来源: Karger

摘要:

Difluoromethylornithine (DFMO) is a nonreversible inhibitor of ornithine decarboxylase (ODC), the initial rate-limiting enzyme in the polyamine biosynthetic pathway. When HL60 leukemic cells were incubated in the presence of concentrations of DFMO from 0.05 m M to 5 m M, there was a concentration-dependent inhibition of ODC activity apparent within 24 h. Likewise, cellular polyamine levels were reduced by the presence of DFMO in a concentration-dependent manner after 4 days. The growth of cells incubated with 0.5 m M or greater was inhibited after 3–4 cell doublings. When the concentration of DFMO was less than 0.5 m M, growth was not inhibited. Methylglyoxal-bis(guanylhydrazone) (MGBG) uptake was enhanced in cells treated with concentrations of 0.05–0.5 m M DFMO, but not enhanced in cells treated with DFMO concentrations of 1 m M or greater. DFMO-induced cellular polyamine depletion does enhance MGBG uptake into HL60 cells, but treatment with high concentrations of DFMO, which deplete polyamines to the extent that growth is inhibited, negate this eff

ISSN:0009-3157    

DOI:10.1159/000238483

出版商:S. Karger AG    

年代:1987

数据来源: Karger

摘要:

The cytotoxic and antitumoral activities of free or bound to bovine serum albumin (BSA) methotrexate (MTX) and the influence of levamisole (LMS) on these were assayed on murine leukemia. Whereas the in vitro cytotoxic action of MTX was reduced by its conjugation to BSA, in vivo a single dose of 15 mg/kg MTX, which lacked therapeutic effect on tumor-bearing mice, increased the mean survival time (MST) of the animals when given as MTX-BSA. Levamisole slightly increased the MST of the tumor-bearing animals when administered as a 10 mg/kg single dose 7 days after the tumor inoculation. We were unable to achieve synergism between LMS and MTX-BSA when measuring MST and the tumor growth evolution.

ISSN:0009-3157    

DOI:10.1159/000238484

出版商:S. Karger AG    

年代:1987

数据来源: Karger

摘要:

Amphotericin B (Amph B), 5-fluorocytosine (5-FC), ketoconazole (KTZ), fluconazole (FLZ), amorolfine (AMOR) and terbinafine (TER) were tested against 3 agents of central nervous system phaeohyphomycosis in vitro and in life-threatening infections in mice. The fungi studied were Cladosporium bantianum, Dactylaria constricta and Wangiella dermatitidis. The broadest protection against this group of fungi in mice was offered by 5-FC followed by Amph B and FLZ, then KTZ. AMOR and TER were inactive in vivo. The results of in vitro susceptibility testing had no predictive value. In contrast, the data obtained from the mouse models should be useful clinically.

ISSN:0009-3157    

DOI:10.1159/000238485

出版商:S. Karger AG    

年代:1987

数据来源: Karger

摘要:

Vidarabine (9-β-D-arabinofuranosyladenine) prepared in a 70% dimethyl sulfoxide vehicle was applied topically to type 1 herpesvirus-induced cutaneous lesions on guinea pigs and athymic nude mice. Treatments were 3 or 5 times daily for 7 days beginning 24 h after virus exposure. Against infections in guinea pigs induced by a thymidine kinase-positive virus strain, either treatment schedule effectively inhibited mean lesion score, lesion size, appearance of new lesions, and reduced lesion virus titers. Therapy was similarly effective against infections in guinea pigs induced by a thymidine kinase-negative virus strain, except that lesion virus titers were somewhat increased in animals treated 3 times daily. Treatment 5 times daily was most efficacious against both virus strains. Treatment 3 times daily of mice infected with a thymidine kinase-negative virus was not effective, but treatment 5 times daily significantly inhibited lesion score and size and reduced lesion virus titer by 37%. Toxicity controls exhibited no signs of skin irritation, although guinea pigs treated 5 times daily experienced some transient weight loss

ISSN:0009-3157    

DOI:10.1159/000238486

出版商:S. Karger AG    

年代:1987

数据来源: Karger

摘要:

Enhanced activity of antiviral agents, when mixed with a penetration enhancer like Azone® (1-dodecylazacycloheptan-2-one) in topical preparations, is well-recognized. These studies were undertaken to investigate whether Azone, per se, has any activity against herpes simplex (HSV) type 1 and type 2 viruses. When HSV-1 and HSV-2 were mixed with 5, 10 and 20% Azone, there was a 1–4.5 log10 decrease in virus titers. The efficacy of 5 and 10% Azone applied topically was evaluated during the treatment of HSV-1 cutaneous infections in guinea pigs. HSV-1 infection was produced by intradermally inoculating guinea pigs with 1077 HSV-1/ml. The mean number of lesions per site was reduced by more than 50% in Azone-treated sites as compared to no treatment (control) sites (p < 0.01). Similarly, the surface area of each lesion in the Azone-treated sites was only 40% of that seen in control sites (p < 0.001). More than 80% of the lesions on Azone-treated sites healed by day 4 as compared to only 3% on control sites (p < 0.001). These data indicate that Azone, a lipophilic chemical, may have antiviral properties when used topical

ISSN:0009-3157    

DOI:10.1159/000238487

出版商:S. Karger AG    

年代:1987

数据来源: Karger