摘要:

Fansimef® is a new antimalarial combination containing pyrimethamine, sulfadoxine and mefloquine in the weight proportions 1+20+10. It has been designed to fight plasmodia resistant to the presently used antimalarial drugs and to counter the development of new resistant forms of the parasites. In the present study tablets containing 25 mg pyrimethamine, 500 mg sulfadoxine and 250 mg mefloquine were used. Six Brazilian volunteers received a loading dose of 2 tablets followed by 20 maintenance doses of 1 tablet at a dosage interval of 7 days. The pharmacokinetic evaluation of each of the three components was based on the assumption of an open linear two-compartment model. After the last maintenance dose the following kinetic parameters were determined for pyrimethamine, sulfadoxine and mefloquine, respectively: elimination half-life = 123, 179 and 550 h; volume of distribution in the postdistributive phase = 2.5, 0.15 and 18.6 1·kg-1, and total systemic clearance = 14.0, 0.64 and 24.0 ml·h-1·kg-1. All these values agree fairly well with those measured in previous single-dose kinetic studies. At steady state, Cmin values of each of the three components generally showed small variations. No unexpected accumulation of any of the three components was observed, indicating that induction or inhibition of metabolic enzymes did not occur during the tr

ISSN:0009-3157    

DOI:10.1159/000238468

出版商:S. Karger AG    

年代:1987

数据来源: Karger

摘要:

The effects of the new monobactam antibiotic aztreonam on platelet function and blood coagulation were evaluated both in vitro and ex vivo. In the in vitro studies carried out on platelets from 6 healthy volunteers, therapeutic concentrations of aztreonam had no effect on platelet function. Aztreonam inhibited platelet aggregation only at concentrations far in excess of those clinically achievable. In the ex vivo studies carried out in 11 patients with aztreonam-sensitive infections, aztreonam, 1 g t.i.d. intravenously, did not produce any effect on platelet function and blood coagulation. We conclude that therapeutic doses of aztreonam appear not to affect haemostasis.

ISSN:0009-3157    

DOI:10.1159/000238469

出版商:S. Karger AG    

年代:1987

数据来源: Karger

摘要:

BMY-28142 was compared in vitro with ceftazidime, cefotaxime and cefoperazone and was found to be more active against Pseudomonas aeruginosa and Staphylococcus aureus. Essentially no effect of increasing inoculum size 100-fold was seen-on MICs with BMY-28142 or ceftazidime; some effect was noted with cefotaxime and cefoperazone.

ISSN:0009-3157    

DOI:10.1159/000238470

出版商:S. Karger AG    

年代:1987

数据来源: Karger

摘要:

In vitro antiamebic activity of selected acridine derivatives has been investigated against Naegleria and Acanthamoeba species. The most active compounds belong to the 9-thioacridanone and the 1,2,3,4-tetrahydro-9-thioacridanone series. In addition, some structure-activity relationships are proposed.

ISSN:0009-3157    

DOI:10.1159/000238471

出版商:S. Karger AG    

年代:1987

数据来源: Karger

摘要:

Fifty-one new synthetic compounds belonging to four different series, namely (1a) substituted aryl-4-(substituted phenyl) succinimide; (1b) N-(substituted methyl)-4-(heterocyclic) succinimide; (2) heterocyclic 4-(5′-nitro-2-furyl) thiazoles; (3) substituted aryl-4-(3′, 4′-dihydroxy phenyl) thiazoles, and (4) phenyl-N, N-1,2,3-bis-methoxy carbonyl guanidines were screened for antituberculous activity using a conventional broth dilution test (BDT) and a liquid scintillation radiometric method (LSRM). Eight compounds showed in vitro activity. LSRM showed 100% agreement with BDT. LSRM is completed within 60 h, while BDT requires 8–9 days. Unlike BDT, LSRM allowed one to measure the graded changes in the metabolism and the growth rate of Mycobacterium tuberculosis in response to various concentrations of the drug. It permits the measurement of the relative prolongation of the replication time by the drug or the test compound. With LSRM it was possible to detect the phase of growth during which the test compound shows or begins its antituberculous activity. It improves our understanding of the antituberculous activity of the test compound and hence is more advantageous. It is rapid, reliable, quantitative and more sensitive than BDT. LSRM is thus suitable for the evaluation of ne

ISSN:0009-3157    

DOI:10.1159/000238472

出版商:S. Karger AG    

年代:1987

数据来源: Karger

摘要:

The in vitro activity of difloxacin (A-56619) and A-56620, two new aryl-difluoroquinolones, was compared to that of other new quinolones and several parenteral and oral antimicrobial agents. A-56620 inhibited 90% of Enterobacteriaceae at ≤1 μg/ml, Staphylococcus aureus 0.25 μg/ml, hemolytic streptococci 2 μg/ml, Pseudomonas aeruginosa 2 μg/ml, Bacteroides sp. and Clostridium at 8 μg/ml.A-56620 was equal or 2-fold more active than norfloxacin and ofloxacin, and 2–8-fold less active than ciprofloxacin. Difloxacin had similar in vitro activity with many isolates but usually was 2–8-fold less active than A-56620. Both agents inhibited β-lactamase positive Haemophilus influenzae (MIC 0.015 μg/ml)and Neisseria gonorrhoeae (MK ≤0.008 μg/ml).Both agents were more active against streptococci and Streptococcus pneumoniae than norfloxacin, ofloxacin and enoxacin, but not more active than ciprofloxacin. They inhibited Enterobacter cloacae, Citrobacter freundii and Serratia marcescens resistant to cephalosporins and methicillin-resistant S. aureus and Staphylococcus epidermidis. Spontaneously resistant mutants were seen with Enterobacteriaceae, P. aeruginosa and S. aureus at a frequency similar to that found for other new quinolones. These agents show overall in vitro activity comparable to other quinolones in clinical trial or recently approved f

ISSN:0009-3157    

DOI:10.1159/000238473

出版商:S. Karger AG    

年代:1987

数据来源: Karger

摘要:

The frequency of selection of resistant variants by 10 different broad-spectrum β-lactam derivatives was evaluated for 10 clinical Enterobacter cloacae isolates. With respect to most penams or cephems, resistant variants could be selected up to 8- or 32-fold the MIC, respectively. However, with cefpirome as the selecting agent resistant variants were obtained only at twice the MIC, whereas resistant variants were barely detectable with temocillin and not detectable in any case with imipenem. The variants exhibited cross-resistance between penams and cephems including aztreonam, but not to temocillin and imipenem regardless of the β-lactamase amount produced. Enzyme production of the variants ranged from 0.2 U to 19.0 U β-lactamase/mg protein of the cell-free supernatants. Moreover, analysis of the outer membrane protein composition did not reveal marked alterations between wild strains and the corresponding variants. It is evident that ‘overproduction of the chromosomal β-lactamase’ cannot explain entirely phenotypic resistance to broad-spectrum β-lactam compounds, but a lack of porin production, i.e. major outer membrane proteins, cannot provide an explanation for the above

ISSN:0009-3157    

DOI:10.1159/000238474

出版商:S. Karger AG    

年代:1987

数据来源: Karger

摘要:

Fifty non-immunocompromised guinea pigs were infected by the intravenous route with 8,000 blastospores of Candida albicans per gram body weight: 26 were treated orally with the excipient, 12 with itraconazole at 1.25 mg·kg-1 and 12 at 5mg·kg-1, once daily for 14 days starting on the day of infection. Hematology was checked for all animals before infection and on days 7, 14 and 17 after infection. Histopathological examinations were done for 2 animals of each group on days 7, 14 and 17. The infection and the therapeutic efficacy were checked by clinical observation, at autopsy and by cultures of organs. Itraconazole was highly active at both concentrations, resulting in clinical cure, negativation of cultures, normalisation of the blood picture and absence of fungal elements and presence of only small remnants of lesions on days 14 and 17 in some organs. No drug-related side effects were observe

ISSN:0009-3157    

DOI:10.1159/000238475

出版商:S. Karger AG    

年代:1987

数据来源: Karger

摘要:

The effects of lincomycin on the immune system were studied on patients suffering from chronic bronchitis by means of phagocytosis, chemotaxis and natural-killer tests. The tests were performed before and 2, 4, 8, 12 and 24 h after administration of 600 mg lincomycin i.m. in a single dose. The results indicate that lincomycin stimulates phagocytosis, expressed as enhanced superoxide production (O2-), chemotaxis and the activity of natural killer cells, measured on the basis of their ability to perform a lysis on the K 562 tumoral target labelled with 51Cr. The stimulating effects on chemotaxis appear already 2 h after the administration of the drug, while the same effect on phagocytosis and natural-killer activity occurs after 4 h. The maximal stimulating activity on all three parameters can be shown at 8 h and disappears at 24 h.

ISSN:0009-3157    

DOI:10.1159/000238476

出版商:S. Karger AG    

年代:1987

数据来源: Karger

摘要:

Without treatment all mice died after receiving 103Klebsiella pneumoniae by intraperitoneal injection. Nevertheless, it was possible to delay treatment for 12 h and still observe a therapeutic response from im gentamicin (5 mg/kg). This gave initial serum concentrations comparable to clinical levels, which fell rapidly (t½ = 15 min) to reach the limit of detection by 90 min. Courses were given of 3 or 6 doses spaced at different intervals. Irrespective of dosage interval there was a marked fall in bacteraemia with each of the first two doses. Between doses separated by 8 or even 12 h there was no evidence of bacterial multiplication but this was obvious by 24 h. Both the bacteraemic responses and the lengths of survival were best with the 12-hour dosage interval. These results are consistent with other reports of the persistence of antibiotic effects despite undetectable serum concentrations and the compatibility of a substantial dosage interval with a successful therapeutic outcome

ISSN:0009-3157    

DOI:10.1159/000238477

出版商:S. Karger AG    

年代:1987

数据来源: Karger