Drugs online research references
J Pharmacol Exp Ther. 1998 Jul;286(1):29-35.
Pharmacodynamic activities of ciprofloxacin and sparfloxacin in a murine pneumococcal pneumonia model: relevance for drug efficacy.
Bedos JP, Azoulay-Dupuis E, Moine P, Muffat-Joly M, Veber B, Pocidalo JJ, Vallee E.
Clinique de Reanimation des Maladies Infectieuses, Hopital Bichat-Claude Bernard, Paris, France.
We looked for associations between pharmacokinetic (Pk) and pharmacodynamic (Pd) parameters of ciprofloxacin (CPFX) and sparfloxacin (SPFX) and the in vivo efficacy of these antimicrobials in an immunocompetent mouse model of severe Streptococcus pneumoniae pneumonia. Bacterial killing curves recorded in the lungs during the 24 h after single subcutaneous injections of the fluoroquinolones (FQs) in doses ranging from 6.25 to 200 mg/kg were compared with mean Pk/Pd parameters in the serum of the same mice. The impact of the dosing interval on the antimicrobial dose response was evaluated based on the survival of mice treated for 3 days with CPFX (25-200 mg/kg) or SPFX (6.25-50 mg/kg) administered at various intervals from 3 to 24 h. Bacterial killing curves showed that the maximal bacterial decrease achieved in the lungs was correlated, similarly for both FQs, with the area under the curve (AUC) above the minimal inhibitory concentration (MIC) (overall correlation: r = 0.968, P < 10(-4)). CPX attained higher maximal bactericidal effect values, a steeper killing slope and a shorter time to maximal bactericidal effect in comparison with SPX for the highest doses tested. The lower MIC of SPFX compared with CPFX (0.25 vs. 0.75 microgram/ml) and its higher AUC/dose ratio (resulting from a lower serum peak but a longer half-life) translated into a greater area under the bactericidal curve. In the dose fractionation experiments, the Pk/Pd parameter most closely correlated with the survival rate for both FQs was the daily AUC/MIC ratio (r = 0.976, P < 10(-4)). When the AUC/MIC ratio was greater than 160, the probability of a clinical cure was 100%, independently of the dosage schedule.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9655838&dopt=Abstract
J Antimicrob Chemother. 1990 Apr;25(4):605-12.
Influence of ciprofloxacin on leukotriene generation from various cells in vitro.
Knoller J, Brom J, Schonfeld W, Konig W.
Lehrstuhl fur Medizinische Mikrobiologie und Immunologie, Ruhr Universitat Bochum, FRG.
The effect of ciprofloxacin on leukotriene generation from human polymorphonuclear leucocytes (PMN) and the respective lymphocyte, monocyte and basophil (LMB) containing cell fraction has been studied. Furthermore, the influence on the LTB4-receptor expression of PMNL, as well as on the synthesis of 12-hydroxyeicosatetraenoic acid (12-HETE) from human platelets, was analysed. The antibiotic concentrations ranged from 0.5 to 4 micrograms/10(7) cells. Analysis of the generated leukotrienes was performed by high performance liquid chromatography (HPLC). The calcium-ionophore A23187 induced leukotriene generation from PMNs and LMBs was significantly suppressed by preincubation with ciprofloxacin in a dose-dependent manner. Incubation of PMNs with the same concentrations of ciprofloxacin induced an augmentation of the LTB4-receptor expression. Preincubation of human platelets led to a suppression of the calcium-ionophore induced 12-HETE generation at high concentrations (8 and 4 micrograms/10(8) cells) and to an increased synthesis of 12-HETE at lower concentrations (0.5, 1, and 2 micrograms ciprofloxacin/1 x 10(8) platelets).
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2161821&dopt=Abstract
Scand J Infect Dis. 1990;22(2):205-8.
Influence of ciprofloxacin on the colonic microflora in young and elderly volunteers: no impact of the altered drug absorption.
Ljungberg B, Nilsson-Ehle I, Edlund C, Nord CE.
Department of Infectious Diseases, University Hospital of Lund, Sweden.
The colonic microflora was studied before, on the fifth day of dosing, and 2 weeks after a 5-day oral course of ciprofloxacin 500 mg BID given to 7 young and 7 elderly, healthy volunteers. Considerable changes in the aerobic microflora were found, while the effects on the anaerobic bacteria were less pronounced. Despite larger absolute bioavailability of the first dose in the elderly (77 vs. 63%; p less than 0.05), the effect of ciprofloxacin on the microflora was similar in the two groups of volunteers. A higher number of clostridia were detected in faeces from elderly subjects before, during, and after the ciprofloxacin regimen.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2356443&dopt=Abstract
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