Pharmacokinetics of dibromodulcitol in humans: a phase I study.
A combined clinical and pharmacokinetic phase I study of the substituted hexitol dibromodulcitol (DBD), administered as a single oral monthly dose, has been performed. Twenty-three patients with advanced neoplasms received DBD doses ranging from 600 to 1,800 mg/m2 body surface area (BSA). The dose-limiting toxicity was myelosuppression, with both significant granulocytopenia and thrombocytopenia occurring at dose levels of 1,500 to 1,800 mg/m2. The average pharmacokinetic parameters for DBD, calculated on the basis of a one-compartment model with first-order absorption and elimination, include the elimination constant, .005 +/- .002/min; absorption constant, .012 +/- .009/min; and an apparent volume of distribution, 1.03 +/- .4 L/kg. The area under the drug concentration curve (AUC) and the peak drug level (Cmax) were linearly related to the dose administered (P less than .001). The mean AUC was 18.7 +/- 6.1 mmol/L min, and the mean Cmax was 47.1 +/- 16.8 mumol/L when normalized to a DBD dose of 1 gm/m2. The elimination constant was significantly reduced in patients with abnormal hepatic function (P less than .01). The elimination constant was not correlated with renal function. The half-life of DBD in plasma (158 minutes) was considerably shorter than the four-to eight-hour half-life of total radioactivity in plasma measured by previous investigators following the administration of radiolabeled DBD.
D000042:Absorption; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D016026:Bone Marrow Transplantation; D002277:Carcinoma / Q000188:drug therapy / Q000378:metabolism; D003961:Dianhydrogalactitol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D005260:Female; D006207:Half-Life; D006801:Humans; D007700:Kinetics; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000378:metabolism; D008875:Middle Aged; D008936:Mitolactol / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism*; D009362:Neoplasm Metastasis; D012509:Sarcoma / Q000188:drug therapy / Q000378:metabolism; D013997:Time Factors
D003961:Dianhydrogalactitol; D008936:Mitolactol