Pharmacokinetics of dipyridamole in thalasemia

เภสัชจลนศาสตร์ของยาไดพัยริดาโมลในคนไข้ธาลัสซีเมีย

Name: Benjamas Janchawee

MeSH: Administration, Oral

MeSH: Chromatography, High Pressure Liquid

MeSH: Dipyridamole -- Administration & dosage

MeSH: Dipyridamole -- Pharmacokinetics

MeSH: Thalassemia

Abstract: Dipyridamole had been used in alleviating number of clinical symptoms related to cardiovascular disorders. The presumed modulating activities of dipyridamole on platalet function suggest its therapeutic potential for hypoxemic syndrome commonly associated with splenectomized thalassemia patients. The pharanacokinetics data of dipyridamole for proper dosing regimens in thalassemia patients is essentially nonexisted. This study was designed to develop an dHPLC-method for monitoring dipyridamole in human blood: both in the plasma and the red blood cells, and study its pharmacokinetic nature in thalassemia so that an accurate dosage regimen could be develop for very unique group of individuals. Being a compound contains chromophore that produces both UV-(max.280 nm) and fluorescence (max.ex.285 & em.475 nm) spectra of which the molar absorptivity of the latter is very strong and thus its detecting sensitivity at 1 nanogram level had been satisfactory developed. Under the acidic chromatographic condition the silica-base C-18 column is less affected and is highly favorable over other conventional methods that the sample preparation in complex matrix, i.e. human blood can be accordingly simplified. The use of minimal amounts of Pic-B6 (2uM) is recommended in this study against the traditional use of ralatively high concentration of the pairing reagent (i.e.,5MM). This was found to have additional advantages in term of efficiency, reliability and sensitivity. The pharmacokinetics parameters of dipyridamole after a single oral dose of 50mg in 8 thalassemia (4 non-splenectomized & 4 splenctomized) and 4 normal volunteers were accordingly determined. It was found that thalassemia patients could absorb less dipyridamole than normal individuals judging from the smaller AUC in thalassemia. The deviated changes of the internal mileiu in the gastrointestinal tract in thalassemia was believed believed to be the contributing cause of delayed in lag time and Tmax of dipyridamole in blood while the absorption rate nor other related pharmacokinetic parameters were not changed. Dipyridamole seems to stay longer inthe RBC than the plasma as the t(1/2)(...) was longer in the RBC, the site of its therapeutic artion. It was proposed that dosage regimen of dipyridamole could be better derived from the pharmacokinetic data of the RBC rather than the parameters commonly taken from the plasma. This would provide a more acurate monitoring adn better use of dipyridamole in thalassemia.

Mahidol University. Mahidol University Library and Knowledge Center

Address: NAKHONPATHOM

Email: liwww@mahidol.ac.th

Name: Udom Chantharaksri

Role: Thesis Advisors

Name: Suthat Fucharoen

Role: Thesis Advisors

Name: Duangchit Panonvana

Role: Thesis Advisors

Created: 1989

Modified: 2561-04-26

Issued: 2018-04-25

eng

DegreeName: Master of Science

Level: Master's Degree

Descipline: Pharmacology

Grantor: Mahidol University

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