負載磷酸二鈉貝皮質醇微粒之肺遞送藥物動力學研究   全文下載

Pharmacokinetics of Betamethasone Disodium Phosphate-Loaded Microparticle Following Pulmonary Delivery

貝皮質醇（Betamethasone, BTM）為一肺部疾病之治療藥物；而磷酸二鈉貝皮質醇（Betamethasone disodium phosphate, BDP）為BTM的前驅藥，在投藥後會快速轉變成BTM。在本研究中以大白兔為實驗動物，載藥物BDP之幾丁聚醣微粒（chitosan microparticle, CM）經肺投藥（ITp）後，研究藥物吸收及分佈情形。此外，進行靜脈注射BDP溶液（IV）及經肺投予BDP溶液（ITs）之研究以作為比較。研究中所用載藥10%之BDP-CM之微粒特性：粒徑分佈狹小（2.76 ± 0.25 μm），表面電位帶正電（40.23 ± 1.98 mv）及振實密度低（0.257 ± 0.106 g/cm3）。雖然三種給藥之藥物排除半衰期（half-life, t1/2）及藥物平均滯留時間（mean resident time, MRT）及生體可用率並無統計差異，但有其趨勢存在。經由3種投藥方式（ITp, ITs and IV），血液（肺組織）的t1/2值分別為236 (220), 153 (141) and 148 (92) 分鐘，而血液（肺組織）的MRT值則分別為376 (355), 231 (227) and 217 (150) 分鐘。BDP-CM經肺投藥後，其BTM的相對（肺）生體可用率及絕對生體可用率分別為222%（ITs當作100%）及72%（IV當作100%）。因此，有適當粒子特性的BDP-CM經肺投藥於肺部也可達到較高的生體可用率及較長的藥物滯留時間。"

Betamethasone (BTM) is a therapeutic agent for the treatment of pulmonary diseases. Betamethasone disodium phosphate (BDP) is a prodrug of BTM and is rapidly converted into BTM after dosing. In this study, intratracheal administration of the dry powder (ITp) of BDP-chitosan microparticle (BDP-CM) was investigated to determine the drug absorption and disposition in New Zealand white rabbits. In addition, intravenous injection (IV) and intratracheal instillation (ITs) of BDP solution were also investigated. The investigated 10% drug-loaded BDP-CM had a narrow size distribution (2.76 ± 0.25 μm), positive zeta potential (40.23 ± 1.98 mV) and low tap density (0.257 ± 0.106 g/cm3). There were no significant differences in AUC, half-life (t1/2) and MRT (mean resident time) among the three delivery routes (p > 0.05), the pharmacokinetics of the three routes could be further evaluated to determine their effects. The t1/2 of ITp, ITs and IV were 236 ± 6 (mean ± SEM), 153 ± 16 and 148 ± 12 min determined from plasma levels, and 220, 141, and 92 min, determined from lung levels, respectively. The MRT of ITp, ITs and IV were 376 ± 138, 231 ± 21 and 217 ± 18 min, determined from plasma levels, and 355, 227, and 150 min, determined from lung levels, respectively. The relative lung and absolute bioavailabilities of BTM for ITp were 222% (ITs as 100%) and 72% (IV as 100%), respectively.