Pharmacokinetics and metabolism of cyclophosphamide administered after total body irradiation of bone marrow transplant recipients.

High-dose cyclophosphamide is used immediately after total body irradiation (TBI) in conditioning for bone marrow transplantation (BMT). Possible interactions of the two treatment modalities were sought by measuring the blood pharmacokinetics of CP and 4-hydroxy-cyclophosphamide (4-HOCP) in patients undergoing BMT. There was a non-significant trend to a shorter half-life of CP compared to reported values. Exposure to 4-HOCP, the major metabolite of CP, did not appear to be altered by prior TBI of the patient.

Unaltered pharmacokinetics after the administration of high-dose etoposide without prior dilution.

The pharmacokinetics of etoposide following a new method of administration was determined. Undiluted etoposide was given at a dose of 30 mg/kg as part an intensified conditioning regimen prior to bone marrow transplantation. A terminal half-life of 3.4 +/- 0.7 h and a volume of distribution of 15.4 +/- 9.6 l were found (n = 8); the AUC was 764 +/- 302 micrograms h ml-1. As compared with those obtained in other pharmacokinetic studies using etoposide diluted in normal saline, our data reflect full systemic bioavailability and unaltered pharmacokinetics. The application of undiluted etoposide makes the therapy easier and less time-consuming and avoids a high fluid volume and a high saline load.