Kotsiou A, Diamanti E, Potamianou A, Parara H, Vovou J, Perisanidis C, Tes C, Tesseromatis C
Department of Pharmacology, University of Athens, Athens, Greece.
Eur J Drug Metab Pharmacokinet. 2008 Jul-Sep;33(3):173-9. doi: 10.1007/BF03191115.
The aim of this study was to determine whether the co-administration of acenocoumarin as anticoagulant and certain quinolones, i.e., cefapirin, pefloxacin and ciprofloxacin increased the levels of the given antibiotics and whether this resulted in a prolongation of prothrombin time. Seventy male albino Wistar rats aged 8-10 weeks and weighed 170 +/- 14 g were used and divided into seven groups (I, II, III, IV, V, VI, VII: n=10). The rats in group I received cefapirin via 1 g/kg/8h im injection. Group II received cefapirin via of 1 g/kg/8h im injection and 0.1 mg/kg/24h p.o. acenocoumarin. Group III received ciprofloxacin 0.18 mg/kg/24h im. Group IV received ciprofloxacin 0.18 mg/kg/24h im and 0.1 mg/kg/24h p.o. acenocoumarin. Group V received 10 mg/kg/24h pefloxacin im. Group VI received 10 mg/kg/24h pefloxacin im and 0.1 mg/kg/24h p.o. acenocoumarin while Group VII received only acenocoumarin 0.1 mg/kg/24h p.o. Drug administration was performed over a total of 5 doses in order to obtain steady state concentrations in the plasma and tissues. The animals were sacrificed by decapitation 2 h after the last antibiotic administration. Prothrombin time and antibiotic concentrations in the serum, femur and mandible were assessed. In the study, all the antibiotics were found to prolong prothrombine time following acenocoumarin administration. In addition, perfloxacin and ciproflaxin concentrations were increased in the serum and mandible after acenocoumarin treatment. Cepafirin levels remained unaffected after the administration of this anticoagulant. In conclusion, anticoagulant and quinolone co-administration led to significant pharmacokinetic interactions. Thus particular attention should be paid in the case of these drugs being used in combination in clinical practice.
本研究的目的是确定作为抗凝剂的醋硝香豆素与某些喹诺酮类药物（即头孢匹林、培氟沙星和环丙沙星）联合使用是否会提高给定抗生素的水平，以及这是否会导致凝血酶原时间延长。选用70只8 - 10周龄、体重170±14 g的雄性白化Wistar大鼠，分为七组（I、II、III、IV、V、VI、VII：n = 10）。I组大鼠通过1 g/kg/8h肌肉注射给予头孢匹林。II组通过1 g/kg/8h肌肉注射给予头孢匹林，并通过口服给予0.1 mg/kg/24h醋硝香豆素。III组通过肌肉注射给予0.18 mg/kg/24h环丙沙星。IV组通过肌肉注射给予0.18 mg/kg/24h环丙沙星，并通过口服给予0.1 mg/kg/24h醋硝香豆素。V组通过肌肉注射给予10 mg/kg/24h培氟沙星。VI组通过肌肉注射给予10 mg/kg/24h培氟沙星，并通过口服给予0.1 mg/kg/24h醋硝香豆素，而VII组仅通过口服给予0.1 mg/kg/24h醋硝香豆素。为了在血浆和组织中获得稳态浓度，总共进行5次给药。在最后一次抗生素给药后2小时，通过断头处死动物。评估血清、股骨和下颌骨中的凝血酶原时间和抗生素浓度。在该研究中，发现所有抗生素在给予醋硝香豆素后均会延长凝血酶原时间。此外，醋硝香豆素治疗后，血清和下颌骨中培氟沙星和环丙沙星的浓度升高。给予这种抗凝剂后，头孢匹林水平未受影响。总之，抗凝剂与喹诺酮类药物联合使用会导致显著的药代动力学相互作用。因此，在临床实践中联合使用这些药物时应特别注意。
