How is the oral bioavailability of ketoconazole impacted by pH levels?

The oral bioavailability of ketoconazole is significantly affected by pH levels in the gastrointestinal tract. Ketoconazole is a weakly basic imidazole derivative, which means that it requires an acidic environment to be adequately solubilized and absorbed.

In low pH environments, such as the stomach, ketoconazole is more soluble, leading to increased absorption and ultimately greater bioavailability. Conversely, in high pH environments, such as those found in the intestines after consuming antacids or in individuals with conditions that affect stomach acidity, ketoconazole becomes less soluble. As a result, its absorption decreases, leading to lower bioavailability. Therefore, the relationship between pH and the solubility of ketoconazole directly affects its absorption characteristics.

This understanding underscores the importance of considering dietary factors and the concurrent use of antacids when prescribing ketoconazole, as these can create a context of increased pH and significantly impact the drug's efficacy.