Penetration of teniposide (VM-26) into human intracerebral tumors. Preliminary observations on the effect of tumor type, rate of drug infusion and prior treatment with amphotericin B or oral glycerol.
Thirty-four consenting patients received VM-26 50-100 mg/m2 I.V. before surgical resection of intracerebral tumor, and drug was measured using a high pressure liquid chromatographic technique. Sufficient tumor for analysis was obtained from 29 patients. Brain metastases (13 patients) had higher concentrations of VM-26 than did gliomas (13 patients). Concentrations were comparable in brain metastases and meningiomas (3 patients). Prolonged (24 h) infusion of VM-26 did not appear to result in higher tumor drug concentrations in 5 patients than did rapid (1 h) infusion in 24 patients. Pretreatment with Amphotericin-B 10 mg/m2 12 h and 1 h before VM-26 did not appear to have any effect on VM-26 uptake into 4 intracerebral tumors, although data were limited, and VM-26 concentrations were very high in 1 metastasis. Pretreatment with oral glycerol 500 mg/kg 18 h, 12 h, 6 h, and immediately before I.V. VM-26 may have resulted in increased penetration of VM-26 into 9 tumors, although confirmation is required. Amphotericin-B, glycerol, and operative conditions did not appear to alter VM-26 plasma pharmacokinetics.
D000666:Amphotericin B / Q000494:pharmacology; D001254:Astrocytoma / Q000378:metabolism; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D005990:Glycerol / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008579:Meningioma / Q000378:metabolism; D011034:Podophyllotoxin / Q000031:analogs & derivatives*; D013713:Teniposide / Q000008:administration & dosage / Q000378:metabolism* / Q000627:therapeutic use
D000666:Amphotericin B; D013713:Teniposide; D011034:Podophyllotoxin; D005990:Glycerol