Does pH adjustment affect the behavior of medications like lisdexamfetamine?

From the Guidelines

pH adjustment can significantly impact the behavior of medications, including lisdexamfetamine, by altering their ionization state and absorption across cell membranes. The ionization state of a medication is crucial in determining its absorption, with acidic environments increasing ionization and reducing absorption, and alkaline environments decreasing ionization and potentially increasing absorption 1.

Medication Absorption and pH

• In acidic environments, amphetamine compounds like lisdexamfetamine become more ionized, which reduces their absorption across cell membranes.
• Conversely, in alkaline environments, these medications become less ionized, potentially increasing absorption.
• This pH sensitivity applies to many stimulant medications and explains why healthcare providers often recommend taking these medications without acidic juices or large amounts of vitamin C supplements within an hour of dosing.

Clinical Implications

• For optimal and consistent medication effects, patients should maintain consistent dietary habits when taking lisdexamfetamine and avoid significant changes in urinary or gastrointestinal pH around dosing time.
• Consuming acidic foods or beverages (like orange juice or vitamin C supplements) around the time of taking lisdexamfetamine might reduce its effectiveness, while alkaline substances might enhance it.
• However, it's essential to note that the provided studies do not directly address the effect of pH on lisdexamfetamine, but rather discuss the importance of pH in medication absorption and the potential for pH adjustment to affect medication behavior 1.

pH Adjustment in Medication Administration

• The study on pediatric parenteral nutrition complications highlights the importance of considering pH when administering medications, as incompatible medications can precipitate and cause occlusions 1.
• Adding a solution that returns the pH of the crystallized medication back into the normal range may dissolve the precipitate, emphasizing the role of pH adjustment in medication administration.

From the FDA Drug Label

Acidifying and Alkalinizing Agents: Agents that alter urinary pH can alter blood levels of amphetamine. Acidifying agents decrease amphetamine blood levels, while alkalinizing agents increase amphetamine blood levels. Adjust lisdexamfetamine dimesylate capsules dosage accordingly. (2.6,7.1)

pH adjustment affects the behavior of lisdexamfetamine by altering its blood levels.

• Acidifying agents (e.g., ascorbic acid) decrease amphetamine blood levels.
• Alkalinizing agents (e.g., sodium bicarbonate) increase amphetamine blood levels. The dosage of lisdexamfetamine dimesylate capsules should be adjusted accordingly 2, 2, 2.

From the Research

pH Adjustment and Medication Behavior

• The behavior of medications like lisdexamfetamine can be affected by various factors, including pH levels 3, 4, 5, 6, 7.
• However, there is no direct evidence in the provided studies that suggests pH adjustment affects the behavior of lisdexamfetamine.
• Lisdexamfetamine is a prodrug that is therapeutically inactive until metabolized in the body to dextroamphetamine (d-amphetamine) 3, 4, 5, 6.
• The pharmacokinetics of lisdexamfetamine suggest a reduced potential for abuse, and its efficacy has been demonstrated in several studies in adults and children with attention-deficit/hyperactivity disorder (ADHD) 3, 4, 5, 6.

Mechanism of Action

• Lisdexamfetamine is hydrolyzed to l-lysine and active d-amphetamine, which is responsible for the activity of the drug 3, 4, 5, 6.
• The pharmacological action of lisdexamfetamine involves blocking norepinephrine (NE) and dopamine reuptake into presynaptic neurons and promoting the release of NE and dopamine into the extraneuronal space 5.
• The efficacy of lisdexamfetamine has been established in several studies, with significant improvements noted in ADHD rating scales, Clinical Global Improvement scores, and assessments of executive function 4, 6.

Abuse Potential

• Lisdexamfetamine has demonstrated a reduced abuse potential compared to immediate-release d-amphetamine 3, 6, 7.
• A study comparing lisdexamfetamine and dextroamphetamine exposures reported to U.S. poison centers found that lisdexamfetamine may have less abuse potential, especially compared with the immediate-release dextroamphetamine/amphetamine formulation 7.