Eman Mostafa Hamed1, Mohamed Hussein Meabed2, Raghda R S Hussein3, Usama Farghaly Aly4. 1. Department of Clinical Pharmacy, Faculty of Pharmacy, Nahda University, Beni-Suef, Egypt. 2. Faculty of Medicine, Beni- Suef University, Beni-Suef, Egypt. 3. Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt. 4. Faculty of Pharmacy, Minia University, El Minia, Egypt.
Abstract
Background: Deferasirox is the first line of treatment in iron overload. In spite of the many studies concerning the efficacy of deferasirox, some patients remain unresponsive to deferasirox. Methods:One hundred and sixty patients were enrolled in stratified-randomized controlled study. Patients were randomly divided into four regimens, group I (n = 40) received 30 mg/kg deferasirox, group II (n = 40) received 20 mg omeprazole and 30 mg/kg deferasirox, group III (n = 40) received 400 mg vitamin E and 30 mg/kg deferasirox and group IV (n = 40) received 420 mg silymarin and 30 mg/kg deferasirox. Blood specimens were collected from each patient for up to 24 h, and then plasma deferasirox concentrations were inspected. Results:Silymarin, Vitamin E, and omeprazole significantly increased the peak plasma concentration of deferasirox (P < 0.001) by 27.9, 14.9 and 2.4 fold, respectively, as compared to deferasirox alone. The bioavailability of deferasirox was improved up to 3.03, 3.57, and 4.98-fold, respectively, following administration of omeprazole, vitamin E, and silymarin compared to deferasirox alone. Conclusion:Silymarin, vitamin E, and omeprazole represent promising adjuvant therapy to improve the chelation efficacy of deferasirox that might also be further applied to enhance the pharmacokinetics of deferasirox to overcome the lack of response.
RCT Entities:
Background: Deferasirox is the first line of treatment in iron overload. In spite of the many studies concerning the efficacy of deferasirox, some patients remain unresponsive to deferasirox. Methods: One hundred and sixty patients were enrolled in stratified-randomized controlled study. Patients were randomly divided into four regimens, group I (n = 40) received 30 mg/kg deferasirox, group II (n = 40) received 20 mg omeprazole and 30 mg/kg deferasirox, group III (n = 40) received 400 mg vitamin E and 30 mg/kg deferasirox and group IV (n = 40) received 420 mg silymarin and 30 mg/kg deferasirox. Blood specimens were collected from each patient for up to 24 h, and then plasma deferasirox concentrations were inspected. Results:Silymarin, Vitamin E, and omeprazole significantly increased the peak plasma concentration of deferasirox (P < 0.001) by 27.9, 14.9 and 2.4 fold, respectively, as compared to deferasirox alone. The bioavailability of deferasirox was improved up to 3.03, 3.57, and 4.98-fold, respectively, following administration of omeprazole, vitamin E, and silymarin compared to deferasirox alone. Conclusion:Silymarin, vitamin E, and omeprazole represent promising adjuvant therapy to improve the chelation efficacy of deferasirox that might also be further applied to enhance the pharmacokinetics of deferasirox to overcome the lack of response.
Entities:
Keywords:
Deferasirox; pharmacokinetic; silymarin; thalassemia Major; vitamin E