STUDIES ON THE GASTROINTESTINAL ABSORPTION OF PHOSPHOCITRATE, A POWERFUL CONTROLLER OF HYDROXYAPATITE FORMATION

被引:7
作者
COOPER, CM [1 ]
SALLIS, JD [1 ]
机构
[1] UNIV TASMANIA,BOX 252C,HOBART,TAS 7001,AUSTRALIA
关键词
PHOSPHOCITRATE; ORAL BIOAVAILABILITY; CALCERGY; INTESTINAL PERFUSION; PORTAL BLOOD; METABOLISM;
D O I
10.1016/0378-5173(93)90053-I
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
In situ gastrointestinal perfusion and a chemical induced subcutaneous calcergy model were used to examine the oral bioavailability of the potent calcification inhibitor, phosphocitrate (PC). Formation of calcergic plaques was observed to decrease by approx. 34% when 450 mg PC/kg body weight per day was given to rats by gavage. An equivalent response was observed when only 10 mg PC/kg per day was given intraperitoneally thus indicating reduced bioavailability of the compound by the oral route. Luminal metabolism of PC did not contribute significantly to its overall poor oral bioavailability. Data derived from perfusion of in situ isolated intestinal segments with PC concentrations from 5 to 20 mM indicated luminal absorption by a passive transport process. Studies with radiolabeled PC confirmed the presence of small amounts of [ C-14]PC and [C-14]citrate in portal blood. It was concluded that the membrane transport characteristics for PC were limiting transfer and that a possible future improvement might arise through the incorporation of a lipophilic moiety into the molecule.
引用
收藏
页码:165 / 172
页数:8
相关论文
共 30 条
[1]   ISOTOPIC AND KINETIC STUDIES OF MECHANISM OF HYDROLYSIS OF SALICYL PHOSPHATE - INTRAMOLECULAR GENERAL ACID CATALYSIS [J].
BENDER, ML ;
LAWLOR, JM .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1963, 85 (19) :3010-&
[2]   A NEW PERSPECTIVE ON THE ANTIATHEROSCLEROTIC ACTIVITY OF CA-2+-CHANNEL BLOCKERS [J].
BLOCK, LH ;
EMMONS, LR .
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, 1990, 20 (03) :236-238
[3]   DISPOSITION AND NEPHROTOXICITY OF 3-AMINO-1-HYDROXYPROPYLIDENE-1,1-BISPHOSPHONATE (APD), IN RATS AND MICE [J].
CAL, JC ;
DALEYYATES, PT .
TOXICOLOGY, 1990, 65 (1-2) :179-197
[4]   HYDROCARBON SPECIFICITY FOR TRANSPORT ON THE TRICARBOXYLATE TRANSPORTER OF RAT-LIVER MITOCHONDRIA [J].
CHEEMADHADLI, S ;
HALPERIN, ML ;
DUPERROUZEL, PR ;
LEZNOFF, CC .
CANADIAN JOURNAL OF BIOCHEMISTRY, 1980, 58 (10) :804-808
[5]   INHIBITION OF BASIC CALCIUM-PHOSPHATE CRYSTAL-INDUCED MITOGENESIS BY PHOSPHOCITRATE [J].
CHEUNG, HS ;
SALLIS, JD ;
MITCHELL, PG ;
STRUVE, JA .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1990, 171 (01) :20-25
[6]  
CLAEYS D, 1989, J BIOL CHEM, V264, P14627
[7]  
DAVISON KL, 1989, INTERMEDIARY XENOBIOTIC METABOLISM IN ANIMALS : METHODOLOGY, MECHANISMS AND SIGNIFICANCE, P315
[8]   DRUG ABSORPTION .I. AN IN SITU RAT GUT TECHNIQUE YIELDING REALISTIC ABSORPTION RATES [J].
DOLUISIO, JT ;
BILLUPS, NF ;
DITTERT, LW ;
SUGITA, ET ;
SWINTOSKY, JV .
JOURNAL OF PHARMACEUTICAL SCIENCES, 1969, 58 (10) :1196-+
[9]   POTASSIUM-PERMANGANATE INDUCED CALCERGY - MODEL TO STUDY THE EFFECTS OF DRUGS ON HYDROXYAPATITE CRYSTAL DEPOSITION [J].
DOYLE, DV ;
DUNN, CJ ;
WILLOUGHBY, DA .
JOURNAL OF PATHOLOGY, 1979, 128 (02) :63-+
[10]   EXPERIMENTAL ANTIARTERIOSCLEROTIC EFFECTS OF CALCIUM-ANTAGONISTS [J].
FLECKENSTEIN, A ;
FLECKENSTEINGRUN, G ;
FREY, M ;
THIMM, F .
JOURNAL OF CLINICAL PHARMACOLOGY, 1990, 30 (02) :151-154