The University Record, July 19, 1993

Cellulose derivative offers new way to fight cholesterol

By Sally Pobojewski
News and Information Services

A high molecular weight cellulose derivative may turn out to be a safe and highly effective new drug for lowering cholesterol, according to Jennifer B. Dressman, associate professor of pharmaceutics and leader of research on the compound at the College of Pharmacy.

Three studies conducted at the Clinical Research Center showed that the compound was just as effective at lowering cholesterol as most prescription drugs currently on the market and did not produce any of the serious side effects commonly caused by these drugs, according to Dressman.

Results of the studies were published in the June 14 issue of the Archives of Internal Medicine.

The cholesterol-lowering compound, a high molecular weight hydroxypropylmethylcellulose called HPMC was developed by Dow Chemical Co. scientists. HPMC is formed from natural cellulose extracted from wood pulp, which is then derivatized. Other forms of HPMC currently are marketed as food additives to thicken cheesecakes, puddings and other food products.

Dressman and Dow’s scientists first demonstrated HPMC’s ability to reduce cholesterol several years ago while they were using the material to study viscosity changes in the gastrointestinal tract.

“This derivative of HPMC increases the thickness or viscosity of material in the upper GI tract causing it to move through the intestine more slowly,” Dressman said. “We believe this increased viscosity interferes with the intestine’s ability to digest and absorb cholesterol.”

To study the compound’s effectiveness as a cholesterol-lowering agent, Dressman’s research team designed and directed three clinical studies. The first study was conducted with 10 healthy young men to see how well they could tolerate large doses of the HPMC derivative. “Side effects were few and limited to the GI tract, while total cholesterol levels fell by an average of 32 percent over a one-week period,” Dressman said.

The second study was an efficacy trial with eight men and four women, all with mildly elevated cholesterol levels. After two weeks, total cholesterol levels in this group were down 22 percent with few side effects reported other than bloating and a feeling of fullness.

“Essentially all the cholesterol reduction in this group was attributed to reductions in LDL, or so-called “bad’ cholesterol,” Dressman said. “LDL levels in these patients fell by 30 percent, while their levels of HDL, or “good’ cholesterol, did not change significantly.”

The third study, conducted with nine women and three men with mildly elevated cholesterol, showed a clear linear relationship between dosage and cholesterol reduction. “We were able to identify a dose level that produced an average 15 percent reduction in LDL cholesterol levels over a one- week period while inducing minimal GI side effects,” Dressman said.

“The dose dependent effect of this HPMC derivative is most impressive,” Dressman added. “It should be possible to regulate cholesterol levels simply by varying the dosage. With its rapid effect, we anticipate that patients could take a high dose initially to lower cholesterol levels and then go on a reduced dose to maintain cholesterol at the lower level.”

Because the derivative of HPMC used in the studies is a very large molecule, it does not pass through the GI tract membrane into the bloodstream, Dressman explained. This eliminates any possibility of serious liver and kidney damage, which sometimes occurs with long-term use of existing anti-cholesterol drugs.

The University and the Dow Chemical Co., which funded the clinical research studies, have applied for patents on the use of the HPMC derivative to lower cholesterol levels. Long-term clinical trials and approval by the Food and Drug Administration will be required before the compound could be available for general use as a cholesterol-lowering agent.

Key researchers participating in the clinical studies include Jeffrey Lee Barnett, assistant professor of internal medicine; Rosemary R. Berardi, associate professor of pharmacy; Sahar Z. Swidan, clinical instructor in pharmacy and research fellow; Cynthia A. Sowle and Stephen W. Tobey, research scientists at Dow Chemical Co.; and Christos Reppas, visiting assistant professor of pharmaceutics from the University of Athens.