August 8, 2012

Combining Alcohol With Some Drugs
Effectively Triples the Dose, Study Says

Uppsala, Sweden—As if liver damage, stomach bleeding and impaired driving aren’t enough reasons to moderate alcohol intake, researchers are providing another motive to be careful about drinking: Alcohol can make some medications up to three times more available to the body, which effectively triples the original dose.

In a report in the American Chemical Society journal Molecular Pharmaceutics, researchers from Uppsala University in Sweden describe the process by which alcohol designed for drinking, ethanol, can increase the amount of nonprescription and prescription drugs that are available to the body after taking a specific dose.

Noting that some drugs don’t dissolve well in the stomach or intestines, researchers sought to find out if ingestion of ethanol made a difference. They created a simulated environment of the small intestine in a preprandial state and measured 22 structurally diverse, poorly soluble compounds for apparent solubility and intrinsic dissolution rate in phosphate buffer pH 6.5 (PhB6.5) and fasted-state simulated intestinal fluid (FASSIF, pH 6.5), with and without ethanol at 5% v/v or 20% v/v. They found that in FASSIF with 20% ethanol, 59% of the compounds demonstrated a more than threefold higher apparent solubility than in the FASSIF without ethanol. The influence of low alcohol levels appeared to be negligible, the authors say.

“Ethanol intake can lead to an unexpected and possibly problematic increase in the bioavailability of drug-like compounds,” the authors write, with a greater effect with acidic substances such as warfarin, tamoxifen and naproxen.

“In conclusion, this study showed that significant effects of ethanol on apparent solubility in the preprandial state can be expected for lipophilic compounds. The results herein indicate that acidic and neutral compounds are more sensitive to the addition of ethanol than to the mixed lipid aggregates present in the fasted intestine,” the authors note.

U.S. Pharmacist Social Connect