Evaluation Of Rat In Situ Intestinal Permeability Study Of Mitragynine

• Main Author: Jagabalan, J.D.Yuvenesan
• Format: Thesis
• Language: English
• Published: 2016
• Subjects: RM300-666 Drugs and their actions
• Online Access: http://eprints.usm.my/32167/1/J.D.YUVENESAN_JAGABALAN_24%28NN%29.pdf; http://eprints.usm.my/32167/

Alkaloid utama dalam daun M. speciosa, mitraginina adalah bertanggungjawab terhadap kebanyakan kesan farmakologi yang telah dilaporkan. Dalam kajian yang telah dijalankan ke atas mikrosom hati, alkaloid ini didapati stabil. Walau bagaimanapun, bioketersediaan mitraginina telah dilaporkan sangat rendah. Kadar penyerapan oral mitraginina yang rendah ini mungkin disebabkan oleh sifat keterlarutan air yang rendah. Di samping itu, kebolehtelapan usus, enzim sitokrom P450 3A4 (CYP3A4), dan sistem eflux p-glikoprotein (P-gp) berperanan penting dalam bioketersediaan oral mitraginina. Oleh yang demikian, penyelidikan ini telah dijalankan untuk menentukan beberapa ciri penyerapan oral dengan menggunakan model perfusat usus tikus in situ. Satu kaedah HPLC-UV yang baru telah dibangunkan untuk pengesanan serentak mitraginina, propranolol dan atenolol untuk kuantifikasi mitraginina dalam sampel perfusat usus tikus in situ. LOQ bagi mitraginina, propranolol dan atenolol adalah masing-masing 2.5, 3.75 dan 3.75 μg/mL. Kejituan dan ketelitian kaedah HPLC-UV bagi mitraginina, propranolol dan atenolol masing-masing adalah di bawah 5%. Mitragynine the principal alkaloid of M. speciosa leaf has been reported to be responsible for most of its pharmacological effects. Mitragynine has been found to be metabolically stable in liver microsomes. However the oral bioavailability of mitragynine has been reported to be very low. The poor mitragynine oral absorption was due but not limited to, its poor water solubility. It is also important to note that the role of intestinal permeability, cytochrome P450 3A4 enzyme (CYP3A4) and p-glycoprotein (P-gp) efflux system on its oral bioavailability could not be ruled out as well. In view of this, work was undertaken to determine some of its oral absorption properties using in situ rat intestinal perfusate model in rats. For mitragynine quantification in in situ rat intestinal perfusate samples, a reliable HPLC-UV analytical method for simultaneous detection of mitragynine, propranolol and atenolol was developed and validated. The LOQ of mitragynine, propranolol and atenolol were 2.5, 3.75 and 3.75 μg/mL respectively. The within day and day to day accuracy and precision for mitragynine, propranolol and atenolol were all below 5% respectively.