DISPOSITION PHARMACOKINETICS OF BEZAFIBRATE IN MAN

被引:55
作者
ABSHAGEN, U
BABLOK, W
KOCH, K
LANG, PD
SCHMIDT, HAE
SENN, M
STORK, H
机构
[1] Medizinische Forschung, Boehringer Mannheim GmbH Mannheim
关键词
bezafibrate; bioavailability; GC-MS; hyperlipoproteinemia; pharmacokinetics;
D O I
10.1007/BF00644963
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The disposition kinetics of bezafibrate, a newly developed drug of great lipid-lowering potency, were investigated in normal male subjects. Five male volunteers received14C-labelled bezafibrate orally in solution, and a further 10 were given the same dose (300 mg) of un-labelled drug as tablets. The concentration of bezafibrate in serum and urine from the latter was determined by GC, and in the former total radioactivity in serum, urine and feces was followed for 48 h, and urinary excretion products were analysed by TLC and GC-MS. Rapid absorption from the gastrointestinal tract led to peak serum levels 30 min and 2 h after administration of solution and tablets, respectively. Since approximately 95% of the administered14C-bezafibrate was excreted in urine within 48 h, and almost all the remainder was detected in feces, absorption can be regarded as complete after administration in solution. The relative optimal bioavailability from the tablets was also complete, since in both cases approximately 50% of the administered dose was detected as unchanged bezafibrate in urine within 24 h by GC in the tablet study, and by TLC in the solution study. Of the decomposition products, more than 20% of the dose was present as glucuronides and the remainder consisted of several more polar compounds, one of which was identified as a hydroxyderivative of bezafibrate. Since the apparent halflife of bezafibrate in serum was 2.1 h, this new drug possesses favourable pharmacokinetic features: rapid and complete absorption, even from tablets, combined with a conveniently short half-life, and clearance which is half renal (56 ml/min) and half metabolic (43 ml/min), giving a total clearance of 99 ml/min. © 1979 Springer-Verlag.
引用
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页码:31 / 38
页数:8
相关论文
共 22 条
[1]  
ADAM O, 1979, MUNCHEN MED WOCHEN, V121, P319
[2]  
ARNTZ HR, 1978, MED KLIN, V73, P1731
[3]  
AYERST CM, 1977, CLIN RES, V25, pA547
[4]   MASS-SPECTRAL ANALYSIS OF GLUCURONIDES [J].
BILLETS, S ;
LIETMAN, PS ;
FENSELAU, C .
JOURNAL OF MEDICINAL CHEMISTRY, 1973, 16 (01) :30-33
[5]  
BOLZANO K, ACTA MED AUSTR
[6]  
CAILLEUX A, 1976, THERAPIE, V31, P637
[7]   GAS-CHROMATOGRAPHIC METHOD FOR DETERMINATION OF BEZAFIBRATE IN SERUM AND URINE [J].
ENDELE, R .
JOURNAL OF CHROMATOGRAPHY, 1978, 154 (02) :261-263
[8]   PHARMACOKINETICS OF DRUGS IN PATIENTS WITH NEPHROTIC SYNDROME [J].
GUGLER, R ;
SHOEMAN, DW ;
HUFFMAN, DH ;
COHLMIA, JB ;
AZARNOFF, DL .
JOURNAL OF CLINICAL INVESTIGATION, 1975, 55 (06) :1182-1189
[9]  
HARTLAPP JH, 1976, NAUNYNSCHMIEDEBE S63, V293
[10]  
HOUIN G, 1975, EUR J CLIN PHARMACOL, V8, P433, DOI 10.1007/BF00562318