新型双氯芬酸钠缓释片的人体相对生物利用度研究

A Study on the Relative Bioavailability of a Novel Sustained-release Diclofenac Sodium Tablet in Healthy Volunteers

８名健康男性志愿者单剂量交叉口服１００ｍｇ受试双氯芬酸钠缓释片、扶他林或ＶｏｌｔａｒｅｎＳＲ１００后，Ｔｍａｘ分别为２．４±１．０、２．１±０．５和４．４±１．８ｈ；Ｃｍａｘ分别为６０２．６±９２．８、３３３７．６±１０８８．２ ７６１．０±３４２．０ｎｇ／ｍｌ；ＭＲＴ分别为１３．２±４．８、２．９±０．８和７．９±１．９ｈ；ＡＵＣ０分别为４８６６．２±６４４．６、５３１４．３±５３４．３和４８２９．１±５８２．８ｎｇ／（ｍｌ－１·ｈ）；双氯芬酸钠缓释片和ＶｏｌｔａｒｅｎＳＲ１００相对于扶他林的生物利用度分别为８８．３±１３．２％和８６．３±１２．６％。另８名志愿者交叉口服受试双氯芬酸钠缓释片（１００ｍｇ，ｐｄ）和扶他林（５０ｍｇ，ｂｉｄ〕，连服５天。Ｃｍａｘ分别为５９３．９±１３４．１、１２４７．８±５２７．５ｎｇ／ｍｌ，峰谷波动率（ＰＴＦ）分别为３．３±１．２、５．３±２．１。本研究将为新型双氯芬酸钠缓释片的临床应用提供依据。

The objective of the study was to compare the novel sustained-release diclofenac sodium tablet(A) with the entericcoated diclofenac sodium(Voltaren , B )and the international marketed diclofenac sodium sustained-release formulation (Voltaren SR100 ,C)in a single oral dose,and to observe it s peak-trough fluctuation(PTF)comparing to B in multiple oral doses. Plasma concentrationswere determined by HPLC. After a single oral dose (100mg) of each of three formulations in a three way crossover design,the Tmaxwas 2. 4 ± 1. 0 、2. 1 ±0. 5and 4. 4 ± 1. 8h;the Cmax was 602. 6 ±92. 8 、3 337. 6 ± 1 088. 2、761. 0 ±342. 0ng/ml;the MRT was 13. 2 ±4. 8 、 2. 9 ±0. 8 and 7. 9± 1. 9h; the AUC0 was 4 866. 2 ±644. 6 、 5 314. 3 ±534. 3 and 4 829. 1 ±582. 8 ng/(m-1 . h) respec-tively. The relative bioavailability of A and C were found to be 88. 3 ± 13. 2% and 86. 3 ± 12. 6% compared with B. In the multipleoral doses study of A and B ,the Cmax. was 593. 9 ± 134. 1and 1 247. 8 ± 527. 5ng/ml,respectively,the PTF of A(3. 3 ± 1. 2)was muchlower than that of B(5. 3 ±2. 1) . It is concluded that A has the distinct characteristics of an effective sustained-release formulationthat will offer clinical advantages of better compliance and tolerability over long term usage.