摘要:

AbstractThe interaction between ciprofloxacin and β‐cyclodextrin leading to the formation of an inclusion complex was studied by phase‐solubility, UV, X‐ray diffractometry, differential scanning, calorimetry differential thermal analysis, infra red and NMR spectroscopy.Partial inclusion of the drug moiety within the β‐cyclodextrin cavity along with an interaction of the carbonyl function of the carboxylic acid of ciprofloxacin with the hydroxyl function of β‐cyclodextrin leaving the piperazine moiety hanging around the narrower rim of the cyclodextrin cavity was established. Change in the crystallinity coupled with improved stability of the drug was also observed on complexation. For improved stability, the complex may be used in place of th

ISSN:1460-8081    

DOI:10.1111/j.2042-7158.1996.tb00536.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

AbstractA combination of local anaesthetic, astringent and antiseptic can be justified for topical application to developing cold sores (herpes labialis) for symptomatic relief and prevention of secondary infection. Virucidal properties have been attributed to a wide range of unrelated compounds. We therefore tested examples of materials likely to be used for the self‐medication of cold sores, for activity against herpes simplex virus type 1 (HSV‐1) to assess whether any additional therapeutic benefits may be gained by their use.Three compounds, cetrimide (antiseptic), lignocaine hydrochloride (local anaesthetic) and zinc sulphate (astringent) were selected to test for in‐vitro activity against HSV‐1. A test using the appearance of cytopathic effects in cell cultures induced by HSV‐1 activity was developed for this purpose.It was established that none of the test compounds achieved statistically significant differences from controls (P>0.05) against HSV‐1 within the cell matrix at concentrations known to be tolerated by the cell cultures. However, cetrimide was shown to be active against extracellular HSV‐1 (P>0.95 in compariso

ISSN:1460-8081    

DOI:10.1111/j.2042-7158.1996.tb00537.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

AbstractVerapamil‐releasing transdermal delivery systems were designed and developed using different ratios of hydroxypropylmethylcellulose (HPMC) K4M, K15M, K100M. Formulations were selected on the basis of their drug‐release content and release pattern. These were evaluated for in‐vitro dissolution characteristics using a Cygnus' sandwich patch holder.The release followed Higuchi kinetics as its coefficient of correlation (r = 0.993–0.997;P<0.001) predominates over first‐order and zero‐order release kinetics. In‐vivo evaluation was carried out on healthy human volunteers (23.12 ± 1.08 y; 63.83 ± 6.54 kg) following the balanced incomplete block design. Dissolution rate constant (K) and data generated from plasma and urine (Cmax, tmax, AUCs, t1/2, K, t1/2a, Ka) were evaluated statistically by two‐way analysis of variance. Statistically excellent correlation was found between percentage of drug absorbed and Cmax, AUC0‐24and AUC0‐∝. The time at which maximum lowering of blood pressure was found coincided with the plasma tmax. A highly significant difference (P0.1) difference was observed.Urinary excretion data is suggested as a simpler alternative to blood level data in studying the kinetics of absorption and derivi

ISSN:1460-8081    

DOI:10.1111/j.2042-7158.1996.tb00538.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

AbstractKetoprofen was iontophoretically delivered to human subjects with a current of 2 mA applied for 80 min (160 mA min) and results were compared with a previous study which had used 4 mA applied for 40 min (160 mA min).Resulting serum levels (about 70 ng mL−1) were reduced tenfold in this study while the total ketoprofen and conjugates excreted in urine (about 400 μg) was reduced to one‐half. The reasons for this difference could be attributed to changes in skin resistance and its recovery, local hyperaemia, or formation of a skin depot, as a function of the magnitude of current and its duration of application. In‐vitro studies with human cadaver skin were also carried out but these‐results were not significantly different from our previous study, when the same total (mA min) application was used.Thus, it appears that the use of total exposure (mA min) to represent drug dosage may be inaccurate, contrary to the common practice in physical therapy

ISSN:1460-8081    

DOI:10.1111/j.2042-7158.1996.tb00539.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

AbstractHoney has been reported to have antifungal activity and so was tested against clinical isolates of the common dermatophyte species which cause tineas in man. A honey with an average level of hydrogen peroxide, and a manuka (Leptospermum scopariumJ. R. and G. Forst, family Myrtaceae) honey with an average level of non‐peroxide antibacterial activity were used. An agar well diffusion assay was used, the contents of the wells being replaced with freshly prepared honey solutions at 24‐h intervals over the 3–4 days of incubation.The lowest concentrations (% v/v, in steps of 5%) of manuka honey with catalase added to remove hydrogen peroxide, and of the other honey (without catalase) showed that inhibition of growth around the wells were, respectively,Epidermophyton floccosum25%, 10%;Microsporum canis25%, 15%;Microsporum gypseum55%, 20%;Trichophyton mentagrophytesvar.interdigitale45%, 15%;Trichophyton mentagrophytesvar.mentagrophytes25%, 15%;Trichophyton rubrum20%, 5% andTrichophyton tonsurans25%, 20%. No inhibitory activity was detected with the other honey at 50% (v/v) with catalase added.The results of this investigation show that the common dermatophytes are sensitive to the antimicrobial activity of honey, indicating that clinical evaluation of honey in the treatment of tineas is warranted. This would determine whether the hydrogen peroxide or the non‐peroxide antifungal agent diffuses better into t

ISSN:1460-8081    

DOI:10.1111/j.2042-7158.1996.tb00540.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

AbstractIt was previously reported that alginate forms a complex with cisplatin, increasing plasma levels of cisplatin and reducing nephrotoxicity but without decreasing in‐vitro antitumour activity. We examined three kinds of cisplatin—alginate complexes with various stoichiometrics (molar ratios of uronic acid of two‐, four‐ and tenfold to cisplatin) to clarify the effect of alginate on the pharmacokinetics of cisplatin‐alginate complex. Plasma levels of cisplatin were maintained at high levels dependent upon the content of alginate.Tissue‐plasma partitioning values of cisplatin (Kp) in several tissues, especially the kidney, at 48 h after administration were repressed by complexation. However, the addition of alginate at molar ratios of uronic acid residue to cisplatin of more than four‐fold had no further effect on plasma level or tissue accumulation of cisplatin. Urinary excretion of cisplatin was accelerated by alginate content up to a ratio of four uronic residues to each cisplatin molecule, while a uronic acid molar ratio of ten showed no further effect.Thus, the effect of alginate on pharmacokinetics of cisplatin is dependent on the amount of alginate, and the optimal content of alginate was around a molar ratio of four, uronic acid

ISSN:1460-8081    

DOI:10.1111/j.2042-7158.1996.tb00541.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

AbstractConcentrations of antibiotics achieved in the body for the treatment of medical device‐associated bacterial biofilm infections are sometimes ineffective. An open chemostat system was used to determine the effectiveness of transient or changing concentrations of ciprofloxacin against planktonic and biofilm bacterial cells mimicking the in‐vivo situation. The rate of kill of mucoidPseudomonas aeruginosaplanktonic and biofilm cells, and the disappearance of ciprofloxacin due to dilution by growth medium, was recorded following the administration of ciprofloxacin to the chemostats.The rate of kill of planktonic cells was higher than that of biofilm cells. The rate constant for loss of ciprofloxacin due to dilution only, mimicking its pharmacokinetic elimination rate, was not significantly different from chemostats containing planktonic cells, but was slightly lower in the chemostat where both planktonic and biofilm cells were growing.The results indicate that in an environment of transient low concentrations of ciprofloxacin, bacteria kill rate is diminished, and that biofilm cells are more resistant to antibiotic action. This suggests that higher doses of the antibiotic may be needed to treat medical device‐related bacterial biofilm infec

ISSN:1460-8081    

DOI:10.1111/j.2042-7158.1996.tb00542.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

AbstractYM‐16638 ([[5‐[[3‐(4‐acetyl‐3‐hydroxy‐2‐propylphenoxy) propyl]thio]‐1,3,4‐thiadiazol‐2‐yl]thio]acetic acid), an orally active leukotriene antagonist, induced a marked decrease in serum alanine aminotransferase (ALT) activity and a decrease in serum cholesterol levels in man and monkeys. To investigate the mechanism of this decrease in serum ALT activity, we measured serum and hepatic ALT activity in cynomolgus monkeys treated with or without YM‐16638.After 4 weeks of treatment with YM‐16638 (60 mg kg−1day−1), serum ALT activity decreased dramatically (83%), concomitant with a decrease in serum cholesterol level (32%). ALT activity in liver homogenate obtained from monkeys treated with YM‐16638 showed a marked decrease of 34%. However, YM‐16638 did not affect serum ALT activity, in‐vitro, even when added in a concentration of up to 10−4M. Conditioned serum from monkeys treated with YM‐16638 did not affect ALT activity in‐vitro. These results indicate that YM‐16638 itself does not directly inhibit ALT activity in the blood and that the inhibitor does not exist in conditioned serum.Addition of the cofactor pyridoxal 5′‐phosphate (PAL‐P) did not restore serum ALT activity to control levels in monkeys treated with YM‐16638. This result indicates that PAL‐P was not the major cause of the decrease in serum ALT. In addition, treatment of HepG2 with YM‐16638 in medium containing [35S]methionine had no effect on the rate of either the synthesis or secretion of ALT.These results indicate that the decrease in serum ALT activity by treatment with YM‐16638

ISSN:1460-8081    

DOI:10.1111/j.2042-7158.1996.tb00543.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

AbstractThe aim of this study was to examine the protective action of (±)‐(E)‐ethyl‐2‐[(E)‐hydroxyimino‐5‐nitro‐3‐hexenamide (FK409), a novel spontaneous nitric oxide releaser, on gastric lesions in experimental rats in comparison with cimetidine, the most popular histamine H2antagonist.Both FK409 and cimetidine, administered orally, inhibited gastric lesion, induced by water immersion stress, dose‐dependently, and their inhibitions were significant at 3.2 and 32 mg kg−1respectively. However, only FK409 (32 mg kg−1, p.o.) significantly inhibited gastric lesion induced by acidified aspirin (76%). Cimetidine (up to 100 mg kg−1, p.o.) showed only 36% inhibition.FK409 has more potent anti‐ulcer activity than cimetidine and in particular shows superior gastric cytoprotection in acidified aspirin‐induced lesions. Thus, FK409 could become a beneficial orally active an

ISSN:1460-8081    

DOI:10.1111/j.2042-7158.1996.tb00544.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

AbstractLipid peroxidation and active oxygen metabolites have been suggested to play an important role in the pathogenesis of acute gastric mucosal injury induced by ischaemia‐reperfusion. On the‐other hand 5‐hydroxytryptamine (5‐HT) has been shown to contribute to gastric mucosal damage. This ulcerogenic action is likely to be mediated through a depressive action on gastric‐mucosal flow via 5‐HT blockade and 5‐HT2‐receptor activation. The aim of this study was to examine the effects of ketanserin a specific 5‐HT2antagonist on gastric injury induced by ischaemia‐reperfusion. The peroxidation of lipids and changes in the activities of related enzymes such as gluthatione peroxidase and myeloperoxidase, as a marker of neutrophil infiltration, were also studied.Intraperitoneal administration of ketanserin prevented post‐ischaemic mucosal injury. The mean ulcer indexes of rats treated with 2.5, 5 and 10 mg kg−1were significantly lower than that of control rats. These protective effects were specifically related to a reduction of neutrophil infiltration. Lipid peroxidation in the stomach was increased by ischaemia‐reperfusion injury and this increase was inhibited by the administration of all the tested doses of ketanserin. In addition, treatment with ketanserin could improve the decreased gluthatione peroxidase activity.These results suggest that selective blockade of 5‐HT2receptors by ketanserin may be effective on ischaemia‐reperfusion gastric injury. The inhibitory effects of ketanserin on neutrophil function and lipid‐peroxidation and the increase of glutathione peroxidase activity seem to contribute significantly to the gastroprotection afforded by ketans

ISSN:1460-8081    

DOI:10.1111/j.2042-7158.1996.tb00545.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY