Drugs online research references
J Pharm Pharmacol. 1998 Jul;50(7):783-8.
Uptake of fluoroquinolones in human monocytes isolated from peripheral blood.
Dorian M, Grellet J, Saux MC.
Pharmacokinetic and Clinical Pharmacy Laboratory, University of Bordeaux II, Faculty of Pharmacy, France.
The aim of this study was to develop a technique for separating monocytic cells in suspension from peripheral blood to measure the intracellular penetration of three fluoroquinolones (ofloxacin, ciprofloxacin and sparfloxacin). Mononucleated cells were isolated from the blood on a density gradient with lymphoprep and purified by a specific technique of adhesion and disadhesion on fibronectin. The monocytes were obtained in suspension with 76.8% purity and 97.9% viability. This was a convenient form for measurement of intracellular accumulation by use of the velocity-centrifugation technique. Intra-monocytic penetration of ciprofloxacin, ofloxacin and sparfloxacin was measured at equilibrium after 30-min incubation in the presence of 16 microg mL(-1) antibiotic. The results revealed low intra-monocytic accumulation of ciprofloxacin (intracellular-extracellular = 1.76) and ofloxacin (intracellular-extracellular = 1.42). The penetration of sparfloxacin was significantly higher (intracellular-extracellular = 2.4). This study confirms the important differences between human immunocompetent cells in terms of their ability to concentrate quinolones. It also underlines the importance of monocyte-macrophage cellular differentiation as a determinant of antibiotic penetration.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9720628&dopt=Abstract
Antimicrob Agents Chemother. 1994 Sep;38(9):1984-90.
Stimulation of genetic instability and associated large genomic rearrangements in Streptomyces ambofaciens by three fluoroquinolones.
Volff JN, Vandewiele D, Decaris B.
Laboratoire de Genetique et Microbiologie, Unite associee INRA, Faculte des Sciences, Universite de Nancy I, Vandoeuvre-les-Nancy, France.
In Streptomyces ambofaciens NSA2002, pigmented wild-type colonies spontaneously give rise to pigment-negative (Pig-) mutants at a frequency of about 0.5%. This genetic instability is related to large deletions which can be associated with amplifications of DNA sequences. The influence of three fluoroquinolones (ciprofloxacin, enoxacin, and norfloxacin) on this property was investigated. At a survival rate higher than 60%, most colonies showed a patchwork phenotype consisting of phenotypically heterogeneous colonies harboring numerous mutant sectors. Moreover, the frequency of Pig- mutants rose to more than 90% at survival rates equal to or higher than 10%. Induced Pig- mutants showed the same phenotypical features as did spontaneous mutants. Most of them also harbored deletions, associated in some cases with DNA amplifications, in two loci of the large unstable region, AUD6 and AUD90 (derived from amplifiable unit of DNA). The size of deletions in induced mutants could rise to 1.5 Mb. These results show that ciprofloxacin, enoxacin, and norfloxacin greatly stimulate genetic instability and the occurrence of DNA rearrangements in S. ambofaciens. Moreover, these three fluoroquinolones had the same rank order for both toxic (i.e., antibacterial) and genotoxic activities. If the antibacterial effect of fluoroquinolones in S. ambofaciens is due to their interference with DNA gyrase, as shown for some other organisms, the genotoxic effect observed could be due to their interaction with this type II topoisomerase. This suggests that DNA gyrase is involved in the process of genetic instability in S. ambofaciens.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7811007&dopt=Abstract
J Appl Bacteriol. 1992 Dec;73(6):484-8.
Effect of polysaccharide interactions on antibiotic susceptibility of Pseudomonas aeruginosa.
Allison DG, Matthews MJ.
Pharmacy Department, Manchester University, UK.
The relative viscosity of Pseudomonas aeruginosa alginate was shown to increase markedly when combined with mucin, Ca2+ ions and the exopolysaccharide from Pseudomonas cepacia. The presence of such a heterodisperse polysaccharide solution significantly reduced the diffusion and hence antimicrobial activity of tobramycin and to a lesser extent ciprofloxacin against Ps. aeruginosa by factors of 90 and 2.5-fold respectively over a 5 h incubation period. The clinical implications of these results are discussed in relation to cystic fibrosis.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1283390&dopt=Abstract
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