The pharmacokinetics of 8 g/m2
methotrexate (MTX) was compared following short (6 h) and long (24 h) infusions of the
drug to 11 children with
osteogenic sarcoma (OS; 42 infusion) and 28 children with
acute lymphoblastic leukemia (ALL: 118 infusions), respectively. No difference was observed in the first-phase half-life, in systemic clearance or in the volume of distribution of the
drug (P greater than 0.05). The concentration of MTX at the end of the infusion was approximately 4-fold higher when the
drug was given over only 6 h. However, patients receiving 24-h infusions had approximately 9-fold higher levels by 24 h after the beginning of the infusion. The area under the data curve from start of the MTX infusion until the beginning of
folinic acid rescue administration was significantly higher in patients with
osteogenic sarcoma (6-h infusions), while the area under the log-data curve was significantly longer in the ALL group (24-h infusions) for the same period. The latter parameter is considered to be characteristic for the concentration-time-effect relationship. The longer duration of MTX administration (with delayed rescue) is thought to be more beneficial from the pharmacokinetic aspect. Patients with
osteogenic sarcoma had significantly lower concentrations of MTX at the end of their last treatment with MTX than at the end of the first infusion. Patients developing MTX toxicity had shorter half-lives of MTX in the beta phase. It is suggested that
cisplatin induced tubular loss of MTX and
folinic acid is responsible for these observations. A wider application of clinical pharmacologic findings in the practice of the administration of
cytostatics is indicated.