An MTP inhibitor that normalizes atherogenic lipoprotein levels in WHHL rabbits

Science

Volumn 282, Issue 5389, 1998, Pages 751-754

  Wetterau, John R ^a   Gregg, Richard E ^a   Harrity, Thomas W ^a   Arbeeny, Cynthia ^a,b   Cap, Michael ^a   Connolly, Fergal ^a,c   Chu, Ching Hsuen ^a   George, Rocco J ^a   Gordon, David A ^a   Jamil, Haris ^a   Jolibois, Kern G ^a   Kunselman, Lori K ^a   Lan, Shih Jung ^a   Maccagnan, Thomas J ^a   Ricci, Beverly ^a   Yan, Mujing ^a   Young, Douglas ^a   Chen, Ying ^a   Fryszman, Olga M ^a,d   Logan, Janette V H ^a   Musial, Christa L ^a   Poss, Michael A ^a   Robl, Jeffrey A ^a   Simpkins, Ligaya M ^a   Slusarchyk, William A ^a   Sulsky, Richard ^a   Taunk, Prakash ^a   Magnin, David R ^a   Tino, Joseph A ^a   Lawrence, R Michael ^a   Dickson Jr , John K ^a   Biller, Scott A ^a   more..

^a BRISTOL MYERS SQUIBB   (United States)

^b GENZYME CORPORATION   (United States)

^c ROYAL COLLEGE OF SURGEONS IN IRELAND   (Ireland)

^d UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

APOLIPOPROTEIN A1; APOLIPOPROTEIN B; CHOLESTEROL; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; LIPID; LIPID TRANSFER PROTEIN; LOW DENSITY LIPOPROTEIN CHOLESTEROL; LOW DENSITY LIPOPROTEIN RECEPTOR; PROTEIN INHIBITOR; TRIACYLGLYCEROL; VERY LOW DENSITY LIPOPROTEIN;

ABETALIPOPROTEINEMIA; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; ATHEROGENESIS; CONTROLLED STUDY; DOSE RESPONSE; DRUG STRUCTURE; DRUG SYNTHESIS; FAMILIAL HYPERCHOLESTEROLEMIA; HAMSTER; HEPATOMA CELL; HUMAN; HUMAN CELL; HYPERLIPIDEMIA; NONHUMAN; ORAL DRUG ADMINISTRATION; PRIORITY JOURNAL; RABBIT; RAT;

ALANINE TRANSAMINASE; ANIMALS; APOLIPOPROTEINS B; ASPARTATE AMINOTRANSFERASES; CARRIER PROTEINS; CHOLESTEROL; CRICETINAE; DISEASE MODELS, ANIMAL; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG DESIGN; DRUG EVALUATION, PRECLINICAL; FLUORENES; HUMANS; HYPERLIPIDEMIAS; HYPERLIPOPROTEINEMIA TYPE II; LIPIDS; LIPOPROTEINS; LIVER; MICE; PIPERIDINES; RABBITS; RATS; TRIGLYCERIDES; TUMOR CELLS, CULTURED;

ANIMALIA; CRICETINAE; ORYCTOLAGUS CUNICULUS; RODENTIA;

EID: 0032561425     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.282.5389.751     Document Type: Article

References (19)

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14. Plasma chemistries for treatments with vehicle and 1, 3, and 6 mg/kg doses of compound 9 were as follows: ALT (U/liter), 73 ± 3 (mean ± SEM),65 ± 5, 75 ± 5, and 71 ± 2, respectively; AST (U/liter), 58 ± 2, 45 ± 3, 58 ± 2. and 59 ± 3; alkaline phosphatase (U/liter), 131 ± 11, 137 ± 1, 135 ± 1, and 131 ± 3; lactic dehydrogenase (U/liter), 156 ± 5, 136 ± 3, 150 ± 3, and 139 ± 5; amylase (U/liter), 1400 ± 300, 1600 ± 100, 1500 ± 200, and 1700 ± 500, gamma glutamyltransferase (U/liter), 2.3 ± 0.7, 2.3 ± 0.2, 1.8 ± 0.4, and 2.2 ± 0.5; glucose (mg/dl), 230 ± 7, 235 ± 8, 194 ± 22, and 199 ± 15; creatinine (mg/dl), 0.4 ± 0, 0.4 ± 0, 0.4 ± 0, and 0.4 ± 0; blood urea nitrogen (mg/dl), 14 ± 1, 14 ± 1, 15 ± 1, and 18 ± 2; total protein (g/dl), 5.4 ± 0.1, 5.5 ± 0.1, 5.7 ± 0.2. and 5.2 ± 0.5; and albumin (g/dl), 3.7 ± 0.1, 3.6 ± 0.1, 3.6 ± 0.1, and 3.6 ± 0.1.
15. The milligrams of triglyceride measured per gram of wet weight liver for treatments with vehicle and 1, 3, and 6 mg/kg doses of compound 9 were as follows: 9.1 ± 0.6 (mean ± SEM), 11 ± 0.3, 18 ± 1.8, and 24 ± 0.4, respectively, at 1 week; 8 ± 0.4, 11 ± 1.1, 12 ± 0.8, and 19 ± 3.4 at 2 weeks; and 9 ± 0.5,11 ± 1.5, 23 ± 3.5, and 19 ± 1.0 at 3 weeks.
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19. The ALT and AST levels of drug-treated rabbits were 54.0 ± 7.4 and 34.6 ± 3.5 U/liter (mean ± SEM) in comparison to vehicle-treated rabbit levels of 48.3 ± 5.2 and 28.8 ± 12.5 U/liter.