Does the Intake of Ethanol Affect Oral Absorption of Poorly Soluble Drugs?

Abstract

The presence of ethanol in gastrointestinal (GI) fluids may increase the solubility of poorly water-soluble drugs. This suggests that intake of ethanol with such compounds could result in increased drug absorption in the stomach and duodenum because of the greater concentration gradient present. To test this hypothesis, in vitro dissolution of 2 poorly soluble compounds (indomethacin and felodipine) was studied in simulated GI rat fluids in the presence or absence of ethanol. Results were used to predict plasma exposure of the compounds using the software PK-Sim. Finally, in vivo plasma exposure in rats was investigated after oral dosing followed by immediate administration of water or ethanol. Despite increased solubility in GI fluids in the presence of ethanol, simulations predicted a negligible effect on absorption. This was confirmed in the rat study where oral intake of indomethacin or felodipine with ethanol did not increase in vivo plasma exposure. A possible explanation for the lack of an effect may be that dilution, absorption, and transfer of ethanol upon arrival in the stomach resulted in intragastric and intraduodenal ethanol concentrations that did not reach the levels required to affect local solubility.

Effect of concomitant oral administration of ethanol on the pharmacokinetics of nicardipine in rats

“…A more than 30% ethanol content may cause pylorospasm in animals and humans, which can delay gastric emptying (Holt, 1981). This effect may increase the T max value after the administration of certain drugs with ethanol and lower the C max owing to much slower and continuous drug transfer from the stomach to the duodenum (Keemink et al, 2019). In this study, there were no significant differences in the T max values whether the ethanol was co‐administrated or not, indicating that there was no delay in gastric emptying.…”

“…Concomitant ethanol intake can alter the pharmacokinetics of poorly soluble drugs. Ethanol can act as a co‐solvent in the gastrointestinal tract, thereby increasing the solubility and absorption rate of drugs (Fagerberg et al, 2015; Keemink et al, 2019). Therefore, an increase in bioavailability is inevitable, which can lead to serious consequences owing to the toxicity of some drugs, especially for those with ethanol‐vulnerable formulations (Lennernas, 2009; Walden et al, 2007).…”