Irinotecan Ciclosporin

Additive renal toxic effects may occur with immunosuppressants (e.g. azathioprine, ciclosporin, tacrolimus), ACE inhibitors, penicillamine, irinotecan and aminoglycoside antibiotics. A deterioration of renal function may even occur after the topical use of NSAIDs. Guidelines are variable for the use of NSAIDs with differing degrees of renal function, as assessed by creatinine clearance measurements. 

Both irinotecan and SN-38 are primarily excreted into the bile by the canalicular multispecific organic anion transporter (cMOAT), a member of the ATP cassette of transporters. Therefore, inhibitors of cMOAT, such as ciclosporin, can reduce the clearance of irinotecan and SN-38 (41,42). 

Ciclosporin reduces the clearance of irinotecan and increases exposure to its active metabolite, SN-38. 

In a phase I study in patients with refractory solid tumours or lymphomas, ciclosporin 5 to 10 mg/kg was given as a 6-hour infusion beginning 3 hours before administration of irinotecan (initial dose 25 mg/m increased to 72 mg/m weekly). Ciclosporin increased the AUC of SN-38 (the active metabolite of irinotecan) by 23 to 630% and reduced irinotecan clearance by 39 to 64%, when compared with historical controls. The effects of ciclosporin on irinotecan may be due to inhibition of irinotecan-and SN-38-related biliary transporters, and this suggestion is supported by a study in Further clinical studies are needed to assess the effects of ciclosporin on the antitumour response and toxicity of irinotecan. 

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