الفهرس 
AcknowledgementOnly 14 pages are availabe for public view
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Abstract
Warfarin is known to have multiple pharmacokinetic and pharmaco-dynamic interactions. It is not uncommon for patients taking warfarin to require therapy with macrolide antibiotics. Patients taking warfarin are often elderly and have several disease states and may be at high risk for respiratory tract infections. Of the macrolide family, erythromycin and clarithromycin have been shown to interact with warfarin, leading to an elevated international normalized ratio (INR). The incidence of over anticoagulation in patients prescribed azithromycin as one of macrolides family stabilized on a warfarin regimen is controversial.
The present study aimed to determine effect of azithromycin on the anticoagulant action of warfarin as well as to study the effect of warfarin on the antibacterial activity of azithromycin and to suggest the readjustment in the dose of azithromycin and warfarin when they are co-administered.
In the first set of experiments, the effect of azithromycin on the anticoagulant activity of warfarin was investigated, to achieve this goal PT, CT and BT were measured.
Firstly, the suitable dose of warfarin for anticoagulant activity in rats was adjusted by trails and from these trails we achieved that the dose 0.05 mg/kg is the submaximal and suitable dose of our study.
Ellagic acid (EA), a plant phenol found in various fruits and nuts, has been documented for its ability to activate coagulation factor XII to trigger intrinsic coagulation system. It was used for induction of hypercoagulable state,
So rats were injected i.p by (EA) 10.5 mg/kg; our results revealed that EA led to highly significant decrease in PT, highly significant decrease in clotting time and bleeding time of rats.
Also, our results showed that animals treated with warfarin (0.05 mg/kg) orally daily for 5 consecutive days before induction of hypercoagulable state led to highly significant increase in PT, highly significant increase in clotting time and bleeding time of hypercoagulable rats in comparison with hypercoagulable rats only.
Also our results revealed that azithromycin had no significant change on the induced hypercoagulable rats which were treated i.p with azithromycin (300 mg/kg) 24 h before induction of hypercoagulable state in comparison with hypercoagulable rats only.
To investigate the effect of azithromycin on the anticoagulant activity of warfarin, rats were administrated a combination of warfarin and azithromycin. The results revealed that combined administration of azithromycin and warfarin in rats had no significant change in PT, CT and BT in comparison with warfarinized rats only.
The second set of this study was conducted to evaluate the effect of warfarin on the antibacterial activity of azithromycin, to achieve this aim we used parameters measured the degree of antibacterial activity as viable bacterial count, neutrophils count, MPO activity, CRP and TNF-alpha.
Infection in rats was induced by i.p injection of E coli (ATCC 8739) 1x108 CFU, the result showed that infected rats had highly significant increase in viable bacterial count, neutrophils count, MPO, CRP, and TNF-alpha in comparison with control group.
To adjust the submaximal dose for antibacterial activity of azithromycin, trails conducted in this study, from these trails, we found that the dose 300 mg/kg is the submaximal dose and suitable for this study.
Our results demonstrated that i.p injection of azithromycin (300 mg/kg) 24 h before induction of infection led to highly significant decrease of viable bacterial count, neutrophils count, MPO, CRP, and TNF-alpha in comparison with infected group only.
Also our results showed that warfarin had no significant change on the induced infection in infected rats in comparison with infected rats only.
To evaluate the effect of warfarin on the antibacterial activity of azithromycin, rats were administrated a combination of warfarin and azithromycin. Our results revealed that combined administration of azithromycin and warfarin in rats had no significant change inviable bacterial count, neutrophils count, MPO, CRP, and TNF-alpha in comparison with infected group treated with azithromycin only.