TY - JOUR
TI - HIGH-MOLECULAR-WEIGHT HYDROXYPROPYLMETHYLCELLULOSE - A
CHOLESTEROL-LOWERING AGENT
AU - DRESSMAN, JB
AU - ADAIR, CH
AU - BARNETT, JL
AU - BERARDI, RR and
AU - DUNNKUCHARSKI, VA
AU - JARVENPAA, KM
AU - PARR, DD
AU - SOWLE, CA and
AU - SWIDAN, SZ
AU - TOBEY, SW
AU - REPPAS, C
JO - Archives of Internal Medicine
PY - 1993
VL - 153
TODO - 11
SP - 1345-1353
PB - AMER MEDICAL ASSOC
SN - 0003-9926, 1538-3679
TODO - 10.1001/archinte.153.11.1345
TODO - null
TODO - Background: We assessed the efficacy of a high-molecular-weight
hydroxypropylmethylcellulose (K8515) as a cholesterol-lowering agent,
the dose-response profile of its action, and the ability of adult
subjects to tolerate its ingestion at effective doses.
Methods: These studies were conducted at the Clinical Research Center of
The University of Michigan Hospitals, Ann Arbor. Efficacy was assessed
in 10 normal and 12 mildly hyperlipidemic subjects in double-blind,
randomized crossover trials of 1 and 2 weeks’ duration, respectively.
The dose-response profile was studied in 12 mildly hypercholesterolemic
subjects in a nonrandomized control trial with doses given in escalating
order. Tolerance was assessed by a questionnaire of adverse effects and
bowel movement habits in all subjects.
Results: We found that 10 g of K8515 ingested in a prehydrated form
three times a day with meals lowered total cholesterol levels by an
average of 1.45 mmol/L (56 mg/dL) (32%) in normal subjects within 1
week. In two studies in subjects with mildly elevated cholesterol levels
(with entry levels ranging from 5.35 mmol/L [207 mg/dL] to 6.70
nunol/L [260 mg/dL]), average reductions of 1.00 mmol/L (39 mg/dL)
(18%) and 1.15 mmol/L (45 mg/dL) (20%) were observed within the same
period. The effect was primarily due to a reduction in low-density
lipoprotein cholesterol levels. Low-density lipoprotein levels in normal
subjects were an average of 1.10 mmol/L (42 mg/dL) (38%) lower after a
week of 10 g of K8515 three times a day with meals, and in the two
studies in subjects with mild hyperlipidemia, the reductions in
low-density lipoprotein levels after 1 week were 0.95 mmol/L (37 mg/dL)
(23%) and 1.05 mmol/L (40 mg/dL) (25%). Although there was a tendency
for high-density lipoprotein cholesterol levels to decrease, this was
significant only in normal subjects. Decreases in cholesterol levels
were not accompanied by any rise in triglyceride levels. Dose-response
studies in those with mildly elevated cholesterol levels indicated that
it is possible to achieve a 15% decrease in low-density lipoprotein
cholesterol levels within 1 week at a dose of 6.7 g three times a day,
with minimal adverse effects.
Conclusions: These results suggest a role for high-molecular-weight
hydroxypropylmethylcellulose in the clinical treatment of mild
hypercholesterolemia.
ER -