摘要
８名男性健康志愿者分别单次口服双氯芬酸钠（ＤＳ）缓释片和双氯芬酸钠肠溶衣片（商品名扶他林；ＤＳ普通片）各１００ｍｇ，用高效液相色谱（ＨＰＬＣ）法测定血中双氯酚酸钠浓度，以确定双氯酚酸钠缓释片的相对生物利用度。９名健康志愿者分别口服双氯芬酸钠肠溶衣片５０ｍｇｑ１２ｈ×５ｄ（连续９次给药）和双氯酚酸钠缓释片１００ｍｇｑｄ×５ｄ（连续５次给药），ＨＰＬＣ法测定血药浓度，以观察稳态血药浓度时双氯酚酸钠缓释片的波动系数（ＦＩ），进一步确定受试片的缓释特征。测定双氯酚酸钠缓释片在ｐＨ７．４磷酸缓冲液介质中１２ｈ释放度并计算双氯酚酸钠缓释片体外释放度与体内吸收速度的相关性。实验结果表明：双氯芬酸钠肠溶衣片和双氯酚酸钠缓释片的ＡＵＣ０－２４ｈ分别为５０１５±７８７和４６６５±３８５μｇ·ｈ·Ｌ－１（Ｐ＞０．０５）；Ｃｍａｘ为２１８６±８３９，５３９±２０１μｇ·Ｌ－１（Ｐ＜０．０１）；Ｔｍａｘ为３．３±１．５，３．７±１．８ｈ（Ｐ＞０．０５）；双氯酚酸钠缓释片的相对生物利用度（Ｆ）为９４．１±８．３％；波动系数（ＦＩ）从双氯酚酸钠普通片的１．７１±０．１１降至缓释片的１．２６±０．２５（Ｐ＜０．０１）；双氯酚酸钠缓释片体外?
Diclofenac sodium sustained-release (DSSR) tablet (produced by Shenzhen Pharmaceutical Factory) 100 mg and diclofenac sodium enteric-coated tablet (Votalin made in Beijing CIBAI-GEIGY Pharma Ltd and maketed in China) 100 mg were orally given to 8 male healthy subjects, respectively. Diclofenac sodium(DS) concentration in plasma was measured by HPLC method to determine relative bioavailability of DSSR. Fluctuation index(FI) of DSSR in DS steady-state concentration was observed after po Votalin 50 mg q12 h×5 d (9 consecutive times) and DSSR 100 mg qd×5 d (5 consecutive times) in 9 male healthy volunteers to farther decide sustained-release feature of DSSR. Relativity between absorption in vivo and dissolution rate in vitro of DSSR was determined by regression absorption fraction vs measurement of dissolution in phosphate buffer (pH 7.4). AUC0-24 , Cmax and Tmax were 5015±787 μg·h·L-1, 2186±839 μg·L-1 and 3.3±1.5 h after po diclofenac sodium enteric_coated tablet and 4665±385 mg·h·L-1 (P>0.05, compared with diclofenac sodium enteric_coated tablet), 539±201 μg·L-1 (P<0.01) and 3.7±1.8 h (P>0.05) after po DSSR, respectively. Relative biolavailability (F) of DSSR was 94.1±8.3%. FI decreased from 1.71±0.11 of diclofenac sodium enteric_coated to 1.26±0.25 of DSSR (P<0.01);Relativity between absorption rate in vivo (73.5% in 12 h ) and dissolution (82.4% within 12 h) in vivo was fine (r=0.9065). The data demonstrated that DSSR possessed good characteristics of sustained_release formulation.
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
1998年第2期86-93,共8页
The Chinese Journal of Clinical Pharmacology
关键词
双氯芬酸钠
缓释片
相对生物利用度
diclofenac sodium sustained-release tablet
diclofenac sodium enteric_coated tablet (Votalin)
HPLC
humans
relative bioavailability
