passages: 834
passages: document
passages: Raising high-density lipoprotein in humans through inhibition of cholesteryl ester transfer protein : an initial multidose study of torcetrapib . OBJECTIVE The ability of the potent cholesteryl ester transfer protein ( CETP ) inhibitor torcetrapib ( CP-529,414 ) to raise high-density lipoprotein cholesterol ( HDL-C ) levels in healthy young subjects was tested in this initial phase 1 multidose study . METHODS AND RESULTS Five groups of 8 subjects each were randomized to placebo ( n=2 ) or torcetrapib ( n=6 ) at 10 , 30 , 60 , and 120 mg daily and 120 mg twice daily for 14 days . Torcetrapib was well tolerated , with all treated subjects completing the study . The correlation of plasma drug levels with inhibition ( EC50=43 nM ) was as expected based on in vitro potency ( IC50 approximately 50 nM ) , and increases in CETP mass were consistent with the proposed mechanism of inhibition . CETP inhibition increased with escalating dose , leading to elevations of HDL-C of 16 % to 91 % . Total plasma cholesterol did not change significantly because of a reduction in nonHDL-C , including a 21 % to 42 % lowering of low-density lipoprotein cholesterol at the higher doses . Apolipoprotein A-I and E were elevated 27 % and 66 % , respectively , and apoB was reduced 26 % with 120 mg twice daily . Cholesteryl ester content decreased and triglyceride increased in the nonHDL plasma fraction , with contrasting changes occurring in HDL . CONCLUSIONS These effects of CETP inhibition resemble those observed in partial CETP deficiency . This work serves as a prelude to further studies in subjects with low HDL , or combinations of dyslipidemia , in assessing the role of CETP in atherosclerosis .
entities: 835
entities: Intervention_Pharmacological
entities: torcetrapib .
entities: 836
entities: Intervention_Pharmacological
entities: cholesteryl ester transfer protein ( CETP ) inhibitor torcetrapib
entities: 837
entities: Intervention_Control
entities: placebo
entities: 838
entities: Intervention_Pharmacological
entities: torcetrapib
entities: 839
entities: Intervention_Pharmacological
entities: Torcetrapib
entities: 840
entities: Outcome_Physical
entities: plasma drug levels
entities: 841
entities: Outcome_Physical
entities: Total plasma cholesterol
entities: 842
entities: Outcome_Physical
entities: nonHDL-C
entities: 843
entities: Outcome_Physical
entities: low-density lipoprotein cholesterol
entities: 844
entities: Outcome_Physical
entities: Apolipoprotein A-I and E
entities: 845
entities: Outcome_Physical
entities: apoB
entities: 846
entities: Outcome_Physical
entities: Cholesteryl ester content
entities: 847
entities: Outcome_Physical
entities: triglyceride
entities: 848
entities: Participant_Condition
entities: healthy
entities: 849
entities: Participant_Age
entities: young
entities: 850
entities: Participant_Sample-size
entities: Five groups of 8 subjects each