摘要:

The pharmacokinetics of sulfadoxine (SULF) and pyrimethamine (PYR) were studied in 7 healthy volunteers after a single oral dose of Fansidar®. A comparison was made between the pharmacokinetics of the components of Fansidar calculated from whole blood and plasma data. The mean whole blood to plasma concentration ratios of SULF and PYR were 0.62 and 0.87, respectively. The elimination half-lives of SULF and PYR were similar in whole blood and plasma. The apparent volume of distribution and clearance of SULF and PYR in whole blood were significantly higher (p < 0.01) than the corresponding plasma values. Because malaria-infected erythrocytes appear to concentrate SULF, it may be more relevant to measure drug concentrations in whole blood rather than in plasma in assessing the antimalarial efficacy of Fansidar

ISSN:0009-3157    

DOI:10.1159/000238499

出版商:S. Karger AG    

年代:1987

数据来源: Karger

摘要:

Any significant change in the pharmacokinetics of an anticancer drug would have a bearing on its therapeutic efficacy and toxicity. Nutritional deficiencies have been shown to affect the pharmacokinetics of a drug. Since malnutrition and undernutrition are widely prevalent in India, the effect of initial nutritional status on the overall kinetics of methotrexate (MTX) administered to cancer patients appeared to be of practical importance. A study of 6 Indian children with malignancies was made to examine the pharmacokinetics of low dose MTX and its relationship to the nutritional status. The results indicate that the relative weight correlates well with the anthropometric parameters, nutritional parameters and dietary intake and may be used as a marker of nutritional status.

ISSN:0009-3157    

DOI:10.1159/000238500

出版商:S. Karger AG    

年代:1987

数据来源: Karger

摘要:

Concommitant concentrations of norfloxacin in serum, urine and prostatic tissue were determined in 12 patients following a single oral dose of 400 mg. Tissue levels ranged from 0.3 to 1.73 mg/kg, and therapeutic concentrations were demonstrable for as long as 8 h following dosage. The mean ratio of tissue to serum concentration was 1.01 ± (SE) 0.13

ISSN:0009-3157    

DOI:10.1159/000238501

出版商:S. Karger AG    

年代:1987

数据来源: Karger

摘要:

The influence of subinhibitory concentrations of clindamycin on opsonization and phagocytosis of Staphylococcus aureus was studied. S.aureus was grown overnight in the presence or absence of one half or one quarter of the minimal inhibitory concentration (MIC) of clindamycin. Radioactively labeled S. aureus was opsonized for various periods of time in different concentrations of normal serum, heated antiserum and serum of patients with agammaglobulinaemia or C3 deficiency. Complement-as well as antibody-dependent phagocytosis of the antibiotic treated S. aureus was significantly enhanced, compared to phagocytosis of the untreated control. Killing experiments showed that clindamycin-treated S. aureus was also better killed by the granulocytes than untreated S. aureus. The mechanism of action is likely to be an increased susceptibility of clindamycin-treated bacteria to antibody- and complement-dependent phagocytosis.

ISSN:0009-3157    

DOI:10.1159/000238502

出版商:S. Karger AG    

年代:1987

数据来源: Karger

摘要:

The susceptibility of Bordetella pertussis (28 strains) and Bordetella parapertussis (6 strains) to 24 antibiotics (penicillin and cephalosporin derivatives, erythromycin, josamycin, cotrimoxazole, imipenem, aztreonam and fosfomycin) was studied by means of the agar dilution method using charcoal horse blood agar. Piperacillin and mezlocillin showed the highest activity (MIC 0.0039–0.00781 μg/ml) against B. pertussis while B. parapertussis was most susceptible to piperacillin (0.03125–0.0625 μg/ml), mezlocillin and latamoxef (0.125–0.25

ISSN:0009-3157    

DOI:10.1159/000238503

出版商:S. Karger AG    

年代:1987

数据来源: Karger

摘要:

The in vitro susceptibility of Mycobacterium avium to RU-28965 alone and in combination with rifampin, isoniazid, and sulfametoxipiridazine was studied by the agar dilution method. The synergistic effect of the RU-28965 with rifampin has been demonstrated. At a concentration of 16 μg/ml or lower of RU-28965, 100% of M. avium strains were inhibited. If 2 μg/ml of rifampin is added the MIC of RU-28965 is lowered to 0.25 μg/

ISSN:0009-3157    

DOI:10.1159/000238504

出版商:S. Karger AG    

年代:1987

数据来源: Karger

摘要:

Fansimef® is a new oral schizonticide which contains pyrimethamine (P), sulfadoxine (S) and mefloquine (M) in a weight ratio of 1:20:10. This antimalarial combination is highly active against multi-resistant Plasmodium falciparum and in vitro studies showed that the resistance development by plasmodia against this combination is considerably delayed. The single-dose pharmacokinetics of the three Fansimef components were investigated in 10 Caucasian volunteers with special emphasis on possible mutual kinetic interactions. For this reason the same subjects received successively tablets of Fansimef (P+S+M), Fansidar® (P+S) and mefloquine alone. Following administration of Fansimef all three components revealed long elimination half-lives (P = 88 h, S = 183 h, M = 437 h) and high binding to plasma proteins (P = 92.5%, S = 87.6%, M = 97.6%). The apparent volume of distribution in the postdistributive phase (VDβ/F) was small for S (0.13 l/kg) but amounted to 2.1 l/kg for P and reached even 11.8 l/kg in the case of M. The systemic clearance (ClST 0.05) were found after administration of Fansidar or M alone. Therefore one can exclude any significant interaction between the single components of the Fansimef combination. In addition, animal studies showed that synergism of the toxicity of the three combination partners can be excl

ISSN:0009-3157    

DOI:10.1159/000238505

出版商:S. Karger AG    

年代:1987

数据来源: Karger

摘要:

In an attempt to test the biological activity of three polymorphic forms of mebendazole (MBZ), called A, B and C, both the LD50 in mice after oral (p.o.) and intraperitoneal (i.p.) administration and the anthelmintic effect of these forms on the enteral and parenteral phases of the nematode Trichinella spiralis were studied. We observed that the polymorphic form A was the least toxic and effective against T. spiralis. The use of the polymorph C is advisable for oral treatment with MBZ in mice, having in mind its lower toxicity with regard to the polymorphic form B and its similar anthelmintic effects.

ISSN:0009-3157    

DOI:10.1159/000238506

出版商:S. Karger AG    

年代:1987

数据来源: Karger

摘要:

A series of derivatives of the antibiotic 1-β-D-arabinofuranosylfhymine (ara T) was synthesized by esterification of the hydroxy group in the 5′-position of the arabinose moiety of the nucleoside with straight-chain and branched-chain carboxylic acids: acetyl-ara T, butyryl-ara T, valeroyl-ara T, pivaloyl-ara T and palmitoyl-ara T. These ara T prodrugs were evaluated for their effect on growth of L5178y mouse lymphoma cells and noninfected BHK-21 cells as well as for their antiviral activity in Herpes simplex virus type 1 and 2 infected BHK-21 cells. All compounds exhibited a marked antiherpes virus activity, whereas the cytostatic activity of two of them, the pivaleric ester and the palmitic ester, was extremely weak. The relative antiviral indices of the 5′-pivaloyl-ara T and 5′-palmitoyl-ara T were found to be much better than the index of ara T

ISSN:0009-3157    

DOI:10.1159/000238507

出版商:S. Karger AG    

年代:1987

数据来源: Karger

摘要:

Histological changes were studied in experimental animals following the intraperitoneal administration of high-dose cisplatin with or without high-dose methotrexate and citrovorum factor. There were pronounced renal toxicities with high-dose (10 mg/kg) cisplatin, particularly involving distal tubules with glomerular congestion. However, lower toxicities were noted with reduced dosage of cisplatin (5 mg/kg) and especially if given once as a single bolus injection instead of a 5-day regimen. Renal and hepatic toxicities were marked with concomitant methotrexate administration leading to hemorrhagic diathesis and shorter survival. However, toxicities were relatively reduced when cisplatin was given as a single bolus injection instead of a 5-day divided course. Such information may prove helpful in future planning of combination chemotherapy in patients with malignancies using these two agents.

ISSN:0009-3157    

DOI:10.1159/000238508

出版商:S. Karger AG    

年代:1987

数据来源: Karger