[Effect of damaged liver parenchyma, renal insufficiency and hemodialysis on the pharmacokinetics of cyclophosphamide and its activated metabolites].
Patients with impaired liver function have a reduced biotransformation rate of the cytostatic agent cyclophosphamide. With pathologically reduced serum cholinesterase activity the half-life of the drug increases from normally 4.3 h to 6.7 h. These patients show significantly lower peak levels of activated cyclophosphamide (4-hydroxy-cyclophosphamide + aldophosphamide). Because of the low renal clearance of cyclophosphamide (16 ml/min) and equally low renal excretion of activated cyclophosphamide amounting to only 1% of the applied dose more than 80% of the drug is still metabolized and the area under the curve of activated cyclophosphamide (cXt) remains relatively constant. No change in the pharmacokinetics of cyclophosphamide and its activated metabolite is observed in an anuric patient. However, an accumulation of toxic, directly alkylating metabolites with a fourfold alkylation rate of plasma proteins is found in this case. Hemodialysis sufficiently eliminated the toxic alkylating metabolites without a measurable influence on the pharmacokinetics of activated cyclophosphamide.
D000368:Aged; D001711:Biotransformation; D002802:Cholinesterases / Q000097:blood; D003520:Cyclophosphamide / Q000378:metabolism*; D005260:Female; D006801:Humans; D007674:Kidney Diseases / Q000378:metabolism*; D007700:Kinetics; D008107:Liver Diseases / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011485:Protein Binding; D006435:Renal Dialysis
D003520:Cyclophosphamide; D002802:Cholinesterases
Einfluss von Leberparenchymschäden, Niereninsuffizienz und Hämodialyse auf die Pharmakokinetik von Cyclophosphamid und seinen aktivierten Metaboliten.