The pharmacokinetics of high dose cyclophosphamide and high dose etoposide

We have studied the pharmacokinetics of single agent high dose cyclophosphamide (HDC) (160-240 mg kg-1) given as repeated intravenous (i.v.) infusions to six patients with small cell lung cancer (SCLC), and HDC (180 mg kg-1) combined with etoposide (750-1000 mg m-2) as repeated i.v. infusions to five patients with SCLC and two patients with teratoma. HDC has a similar pharmacokinetic profile to low dose cyclophosphamide, with a half-life of 4.83 +/- 1.3 h. Repeated administration of HDC produced a small but significant shortening of the half life (P = 0.02). The terminal half-life of high dose etoposide was 7.7 +/- 2 h which is similar to our previous results with low dose etoposide (50-300 mg m-2), but the volume of distribution which was 35.5 +/- 11.6 1. was significantly increased (P less than 0.001). Plasma steady state concentrations of 26.2 +/- 11.7 micrograms ml-1 were achieved. The possible mechanism for the alteration of volume of distribution of etoposide will be discussed.