Anticoagulant-induced changes on antibiotic concentrations in the serum and bones.
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.
Kotsiou
A
A
Department of Pharmacology, University of Athens, Athens, Greece.
Diamanti
E
E
Potamianou
A
A
Parara
H
H
Vovou
J
J
Perisanidis
C
C
Tes
C
C
Tesseromatis
C
C
D000074:Acenocoumarol / Q000494:pharmacology*; D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics; D000925:Anticoagulants / Q000494:pharmacology*; D004347:Drug Interactions; D005269:Femur / Q000737:chemistry*; D007273:Injections, Intramuscular; D008297:Male; D008334:Mandible / Q000737:chemistry*; D011517:Prothrombin Time; D015363:Quinolones / Q000097:blood / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
D000900:Anti-Bacterial Agents; D000925:Anticoagulants; D015363:Quinolones; D000074:Acenocoumarol