Failure of single dose methotrexate followed by citrovorum factor in nonmetastatic gestational trophoblastic neoplasia.

With increasing cost of medical care, newer methods of administering chemotherapy on an outpatient basis are being sought to reduce the need for hospitalization and protracted losses of valuable time for patients with nonmetastatic gestational trophoblastic neoplasia (NMGTN). To achieve this end, two NMGTN patients were treated with a single course of one dose of methotrexate (MTX) followed by multidose Citrovorum Factor (CF) without observing the expected response. Failure to respond appeared to be due to the schedule of administration. Although the dose and plasma concentrations of MTX were considered to be adequate for cell kill, fractionation--as established by conventional schedules of MTX administration--appeared necessary for response by exposing the maximum number of trophoblastic cells to inhibitory levels of MTX during the S-phase of the cell cycle.

Ethanol elimination in the anesthetized dog: intragastric versus intravenous administration.

We computed by linear kinetics predicted equilibrated plasma concentrations, elimination parameters and availability of ethanol for fasting anesthetized dogs who received the same dose (11 mmol/kg) of ethanol twice, once intragastrically and once intravenously. Agreement between predicted (y) and observed (x) equilibrated plasma levels above 3 mmol/l was for intragastric ethanol y = 0.031 + 1.008x (r = 0.973) and for intravenous ethanol y = 0.2 + 0.99x (r = 0.992). Linear elimination (elimination rate, clearance, time of disappearance of half the dose) was significantly slower and Widmark's ratio r was significantly greater for intragastric than for intravenous ethanol. Apparent availability of intragastric ethanol, computed by dividing the intragastric by the intravenous plasma ethanol concentration at zero time (both values extrapolated from the linear portion of the blood alcohol curve), was 0.739 +/- 0.125. Considerable ethanol residuals were present in the stomach four hours after intragastric instillation. We conclude that retention of ethanol in the stomach, probably because of anesthesia, created the apparent differences in elimination of ethanol between intragastric and intravenous administration. Despite gastric retention, decrease of ethanol levels was linear above 3 mmol/l after intragastric instillation.