Abstract
MAEZAWA, S., OHIRA, S., SAKUMA, M., MATSUOKA, S., WAKUI, A. and SAITO, T. Effects of Inducer of Liver. Drug-Metabolizing Enzyme on Blood Level of Active Metabolites of Cyclophosphamide in Rats and in Cancer Patients. Tohoku J. exp. Med., 1981, 134 (1), 45-53 - It was already reported that a masked compound, Cyclophosphamide (Endoxan, EX) undergoes the first-step metabolism by a drug-metabolizing enzyme in liver microsomes, cytochrome P-450. By pretreatment with phenobarbital as an Inducer of P-450, the maximum blood level of active metabolites of EX (normustard-like substances) in normal rats was 2.3 times higher than that in non-treated rats, in conformity with the increase in amount of liver P-450 and in alkylating activity of EX. In YS (Yoshida sarcoma)-bearing rats, the value of liver P-450 went down day by day to 1/2 on the 4th day after inoculation, but it remained normal when animals were pretreated with phenobarbital. In parallel with this, the blood level of normustard-like substances after EX administration was normal or showed a tendency toward increase. In 11 clinical cases pretreated with phenobarbital, the blood level of normustard-like substances 1 to 3hr after EX administration, at the time when it reaches the peak, was 1.5 times higher on an average than that in cases without pretreatment.
