The Effect of Ticagrelor on the Pharmacokinetics of Tacrolimus in Healthy Male Rabbits

الموضوعات

علوم بحتة وطبيعية

الملخص

The effect of Ticagrelor on the Pharmacokinetics of Tacrolimus in healthy Male Rabbits. Introduction: Tacrolimus (TAC) is the most common and widely prescribed immunosuppressant drugs ,used to prevent allograft rejection in patients with transplanted organs or tissues, prevention of graft-versus-host disease ,and for the treatment of moderate to severe atopic dermatitis and and other inflammatory skin diseases. TAC has several properties to be involved in clinically interactions with co-administered drugs and herbal products: " First: TAC exhibits a narrow therapeutic index. " Second: TAC is a potent enzyme inducer of several cytochrome P450 (CYP) isoenzymes. " Finally: TAC is metabolized mainly by CYP3A4, which is one of the Cytochrome P450 enzymes. Variety of drugs may interact with tacrolimus lead to serious side effects or organ rejection, as well as herbal medicines may interact with tacrolimus which leads to potential clinical consequences. Ticagrelor is one of the most drugs used in a patient with Atherosclerosis and had organ transplantation; it appeared to induce or inhibit CYP3A4 activity. Aim: To investigate the effect of TICA on TAC pharmacokinetics in healthy male rabbits at a steady state when taken at the same time. Methodology: An in vivo drug-drug interaction, a randomized, parallel design study was conducted in 12 healthy male rabbits. The study was carried out in one period. In this period, two groups of healthy male rabbits (3.0-3.4 ± 0.7 kg, aged 6-8 months) were enrolled in this study. In the first group, TAC was administered alone as single daily oral dose (0.6 mg/kg) for five days, at the same time, TAC was administered concomitantly with TICA (10 mg/kg) to the second group of rabbits as the first group. Serial blood samples were collected over 7 hours after the last dose of TAC. Chemiluminescent enzyme immunoassay (CLEIA) was used to measure TAC concentration in whole blood. Pharmacokinetic parameters as C max, t max, AUC 0-420, t ½, MRT , and the constant rate of elimination Ke were determined for both groups. Results: Mean of PK parameters of TAC administered alone (Reference Group) or in combination when administered with TICA (Tested group) were; Cmax 22.40 ng/mL versus 28.54 ng/mL, t max 0.875 h versus 1.08 h, Ke 0.9 h-1 versus 0.09 h-1, AUC 0-420 156.78 versus 168.18 ng·h/ml, and t 1/2 8.91 versus 8.43 h. the obtained results demonstrate that Statistically insignificant differences were found in the mean of PK of TAC between the two groups with P > 0.05. Conclusion: In this study and according to our experimental conditions, it has been found that TICA does not affect the pharmacokinetics of TAC. Keywords: Tacrolimus, Ticagrelor, CYP3A4, Drug interaction, Pharmacokinetic.

روابط وملفات

التعريف والنوع

رقم الوثيقة

0b608bce-e02d-4bd4-9ce0-1be2f296565d

رقم العقد

0

نوع الوسائط

Crawler

نوع المحتوى

الرسائل العلمية

صيغة المصدر

رسائل ماجيستير

نوع الملف

pdf text

أسماء الملفات

2103679_1.pdf

بيانات النشر

ترجمة العنوان

دراس تأثير دواء Ticagrelor (TICA) (تيكاجريلور) على حركية دواء Tacrolimus (TAC) (تاكروليمس) في أرانب تجارب ذكور سليمة صحيا

ألقاب المؤلفين

[{"name_ar":"Issam Abu shammala","title_ar":"اشراف","title_en":"Supervision"},{"name_ar":"Yousuf A. Muqat","title_ar":"اعداد","title_en":"Preparation"}]

اللغة

English

المصدر والدورية

اسم المصدر

The Effect of Ticagrelor on the Pharmacokinetics of Tacrolimus in Healthy Male Rabbits

المحتوى والصفحات

عدد الصفحات

0

إشراف وإعداد

الإشراف

Issam Abu shammala

الإعداد

Yousuf A. Muqat

الاقتباسات الببليوغرافية