Pharmacokinetic Profile of Irinotecan in Patients with Chronic Kidney Disease: Two Cases and Literature Review.

Limited pharmacokinetic data exist on the use of irinotecan in patients with reduced glomerular filtration rate (GFR) and no haemodialysis. In this case report, we present two cases and review the current literature. The dose of irinotecan in both patients was reduced pre-emptively due to reduced GFR. The first patient had her irinotecan dose reduced to 50%, but was nevertheless admitted to hospital because of irinotecan-induced toxicity, including gastrointestinal toxicity and neutropenic fever. The dose was reduced further to 40% for the second cycle, however the patient was again admitted to the hospital, and irinotecan was stopped indefinitely. The second patient also had his irinotecan dose reduced to 50% and was admitted to the emergency department for gastrointestinal toxicity after the first cycle. However, irinotecan could be administered in the same dose in later cycles. The AUCs 0-inf of irinotecan and SN-38 in the first patient were comparable to those of an individual receiving 100% dose intensity. The AUCs 0-inf of irinotecan and SN-38 in patient 2 in both cycles were slightly less than aforementioned reference values. Furthermore, clearance values of irinotecan and SN-38 in our patients were comparable to those without renal impairment. In conclusion, our case report suggests that reduced GFR may not significantly affect the clearance of irinotecan and SN-38, but can still result in clinical toxicity. Reduced initial dosing seems indicated in this patient population. Further research is needed to fully understand the relationship between reduced GFR, pharmacokinetics, and toxicity of irinotecan and SN-38.