Altered cyclophosphamide and thiotepa pharmacokinetics in a patient with moderate renal insufficiency

Corine Ekhart, J. Martijn Kerst, Sjoerd Rodenhuis, Jos H. Beijnen, Alwin D.R. Huitema

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

12 Citaten (Scopus)

Samenvatting

Purpose We report a patient with renal insufficiency (creatinine clearance, CLcr = 38 mL/min) who received high-dose chemotherapy with cyclophosphamide (1,500 mg/m2 day-1), thiotepa (120 mg/m2 day-1) and carboplatin (AUC = 5 mg min/mL day -1) for four consecutive days. Methods Blood samples were collected on day 1 and 3 and plasma levels of cyclophosphamide, its active metabolite 4-hydroxycyclophosphamide, thiotepa, its main metabolite tepa and carboplatin were determined. Pharmacokinetic analyses indicated that the elimination of cyclophosphamide, thiotepa, carboplatin, but especially tepa was strongly reduced in this patient, resulting in increased exposures to these compounds of 67, 43, 30 and 157%, respectively, compared to a reference population (n = 24) receiving similar doses. Exposure to 4-hydroxycyclophosphamide increased 11%. Conclusion These results suggest that it may not be necessary to alter the dose of cyclophosphamide in patients with moderate renal impairment. However, because high exposures to thiotepa and tepa have been correlated with increased toxicity, caution should be applied when administering thiotepa to patients with renal insufficiency.

Originele taal-2Engels
Pagina's (van-tot)375-379
Aantal pagina's5
TijdschriftCancer Chemotherapy and Pharmacology
Volume63
Nummer van het tijdschrift2
DOI's
StatusGepubliceerd - jan. 2009
Extern gepubliceerdJa

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