“…The factors responsible for these variations must include rates of absorption and excretion, entero-hepatic re-cycling, plasma protein binding, etc., and few studies have been made of these aspects [Liegler et al, 1967;H alprin et al, 1971;N oble et al, 1975]. Elaborate models of metho trexate metabolism have been proposed [Zaharko et al, 1971;Bischoff et al, 1971], Daily dosage schedules should have been abandoned in the light of clinical confirmation of the theoretical expectation [Van Scott et al, 1964] that intermittent (i.e. weekly) therapy is less hepatotoxic and no less effective [Dahl et al, 1972;Almeyda et al, 1972].…”