Cladribine as a Potential Object of Nucleoside Transporter-Based Drug Interactions

Area of Science:

• Pharmacology
• Immunology
• Neurology

Background:

• Cladribine (Mavenclad®) treats relapsing multiple sclerosis by targeting B and T-lymphocytes.
• Its active form, 2-chlorodeoxyadenosine triphosphate, is generated intracellularly.
• Cladribine's absorption and distribution rely on various nucleoside transporters (NTs).

Purpose of the Study:

• To review nucleoside transporter (NT) inhibitors that may affect cladribine's pharmacokinetics.
• To summarize potential drug interactions impacting cladribine absorption and target cell uptake.
• To provide guidance on optimized administration and drugs to avoid during cladribine treatment.

Main Methods:

• Literature review of nucleoside transporters (equilibrative and concentrative NTs) and ABC efflux transporters involved in cladribine transport.
• Analysis of known inhibitors of these transporters.
• Synthesis of information on potential clinical implications for cladribine therapy.

Main Results:

• Cladribine is transported by ENT1, ENT2, ENT4, CNT2, CNT3, and breast cancer resistance protein.
• Drug interactions involving NT inhibitors can reduce cladribine bioavailability and target cell exposure.
• Clinicians must be aware of medicinal products, lifestyle drugs, and food components that inhibit NTs.

Conclusions:

• Optimized cladribine therapy requires managing transporter-mediated drug interactions.
• Avoiding concomitant NT-inhibiting drugs is essential to maintain cladribine's therapeutic potential.
• Clinician awareness of these interactions is key for effective multiple sclerosis management.