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- Title
Cyclophosphamide pharmacokinetics and dose requirements in patients with renal insufficiency.
- Authors
Haubitz, Marion; Bohnenstengel, Frank; Brunkhorst, Reinhard; Schwab, Matthias; Hofmann, Ute; Busse, Dagmar
- Abstract
Background: Intravenous pulse administration of cyclophosphamide (CYC) has been successfully used for the treatment of various autoimmune diseases. These patients often present with impaired renal function or even end-stage renal failure. Nevertheless, data concerning pharmacokinetics of CYC in renal insufficiency (RI) and on hemodialysis (HD) are rare and contradictory. Methods: The pharmacokinetics of CYC (0.5 to 1 g/m² as a one-hour infusion) were determined in patients with renal involvement of autoimmune diseases. Group A (N = 6) patients had a creatinine clearance (C[sub Cr]) of 25 to 50 mL/min, group B patients' (N = 5) C[sub Cr] was 10 to 24 mL/min, and group C (N = 6) patients had C[sub Cr] values <10 mL/min and HD. Concentrations of CYC in serum, dialysate and urine were measured by HPLC. Twelve previously investigated patients with normal renal function served as controls. Results: Mean clearance (CL) of CYC was significantly reduced with decreased renal function (79 vs. 57 and 47 mL/min, controls vs. A and B, respectively, P < 0.05), but only moderately lower in the patients who received a three-hour HD during the study period (group C, 64 mL/min, NS). This resulted in reciprocal increases in systemic drug exposure (dose corrected AUC was 216, 298, 382 and 266 µg · h/mL · g, controls, A, B and C, respectively). Urinary excretion of CYC was markedly reduced in all patients with RI (renal CL was 14.9 vs. 3.4, 2.4 and 2.1 mL/min, controls vs. A, B and C, respectively, P < 0.001). However, in patient group C, a mean of 22% of administered CYC dose was eliminated by a three hour HD starting seven hours after CYC administration. Individual C[sub Cr] values were significantly (P < 0.001) correlated with renal and systemic CL of CYC, respectively, and negatively correlated with dose corrected AUC. Conclusions: Clearance of CYC is decreased in patients with reduced renal function, thereby resulting in an increased systemic drug...
- Publication
Kidney International, 2002, Vol 61, Issue 4, p1495
- ISSN
0085-2538
- Publication type
Academic Journal
- DOI
10.1046/j.1523-1755.2002.00279.x