Effect of hemodialysis on topotecan disposition in a patient with severe renal dysfunction

The pharmacokinetics of topotecan have been extensively studied in patients with normal renal function and there is one study of patients with mild to moderate renal insufficiency. However, the effect of hemodialysis on topot ecan disposition has not been reported. The objective of this study was to characterize the disposition of topotecan in a patient with severe renal in sufficiency receiving hemodialysis. Topotecan lactone disposition was chara cterized in a patient on and off hemodialysis. The topotecan lactone cleara nce determined after administration of topotecan alone and with hemodialysi s was 5.3 1/h per m(2) vs 20.1 1/h per m(2), respectively. At 30 min after the completion of hemodialysis, the topotecan plasma concentration obtained was greater than that measured at the end of hemodialysis (i.e. 8.0 ng/ml vs 4.9 ng/ml), suggesting a rebound effect. The topotecan terminal half-lif e off dialysis was 13.6 h, compared with an apparent half-life determined d uring hemodialysis of 3.0 h. These results demonstrate that topotecan plasm a clearance while on hemodialysis increased approximately fourfold. Hemodia lysis maybe an effective systemic clearance process for topotecan and shoul d be considered in selected clinical situations (e.g. inadvertent overdose, severe renal dysfunction).