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Biomedical subjects

T L Loo

Publications and source records attributed to T L Loo.

122 records · Page 7Linked to original sources
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Pharmacologic studies of cyclocytidine and arabinosylcytosine in dogs.

Cyclocytidine (cyclo-C) and arabinosylcytosine (ara-C) were compared as to distribution and metabolism in dogs after administration by the intravenous, subcutaneous, intramuscular, and oral routes. After cyclo-C, two metabolites were found in the plasma and urine--a hydrolytic product, ara-C, and its deaminated product, arabinosyluracil (ara-U). The urinary excretion of cyclo-C is rapid; Five hours after parenteral administration, 60% of the given drug is excreted; 45% as cyclo-C, 10% as ara-C, and about 5% as ara-U. In contrast, after similar injections of ara-C, 45% of the drug is excreted; 33% as ara-C and 12% as ara-U. When compared with those in human and mouse tissues, the deoxycytidine deaminase levels in dog tissues are extremely low. This agrees with the finding of low ara-U levels in dog plasma and urine after administering cyclo-C or ara-C. Regardless whether cyclo-C or ara-C is injected, the plasma decay curve of the resultant ara-C is biphasic, with calculated half-lives of 40 min and 2-2.5 hr. However, if ara-C is given, the plasma ara-C peak level is higher. Higher ara-C levels are also maintained throughout the measured 5 hr. There are no differences in pharmacologic disposition after iv, sc, or im administration of ara-C. This is also true for cyclo-C. These findings suggest that for both drugs, the above routes of administration may be equally effective. Neither cyclo-C nor ara-C is well absorbed after oral administration, and the drug concentration in the plasma is too low to be measurable. Whether the dog is fasted overnight or fed, the drug is excreted slowly. In 5 hr. no more than 3% is excreted, and by 12 hr. only 10% is excreted.

Administration, Oral↗
PubMedDate not supplied

Effect of thymidine on the toxicity and antitumor activity of ftorafur.

The effects of thymidine (TdR) on the toxicity and antitumor activity of ftorafur (FT), a 5-FU analog, were determined. The LD10 of FT was 130, 430, and 680 mg/kg, respectively, when FT was administered ip in the following treatment schedules: (a) daily for 9 days, (b) every 4th day for three treatments, and (c) 1 day only. When FT was administered simultaneously with 250 mg/kg of TdR, the LD10 was 13, 62, and 630 mg/kg in the respective treatment schedules. Lethargy was observed in mice when the daily dose of FT was greater than or equal to 150 mg/kg. FT alone was active (% treated/control [T/C] = 153) against ascites P388 murine leukemia only at high, single doses. Simultaneous administration of FT and 250 mg/kg of TdR at or below the LD10 dose of FT resulted in an increase in the antitumor activity to a % T/C of 217 (daily, Days 1-9) and 188 (daily, Days 1, 5, and 9). The activity of FT administered simultaneously with TdR on Day 1 only (%T/C = 142) was lower than that for FT alone. Using a treatment schedule of Days 1, 5, and 9, a TdR/FT mol ratio of greater than or equal to 2.0 seems necessary to achieve an increase in therapeutic value against P388 murine leukemia. This may explain the lack of increase in activity against P388 when 250 mg/kg of TdR was coadministered with FT on Day 1 only. FT alone or coadministered with 250 mg/kg of TdR was equally active against L1210 ascites tumor at doses up to the LD10 with daily treatments on Days 1, 5, and 9 and on Days 1-9; the doses of FT, however, were below those which cause lethargy.

Animals↗
PubMedDate not supplied

Vinblastine given as a continuous 5-day infusion in the treatment of refractory advanced breast cancer.

In an attempt to improve the therapeutic index of vinblastine by maintaining a prolonged, constant plasma level, it was given as a continuous 5-day infusion at 1.4-2.0 mg/m2/day. Among the 30 evaluable patients with advanced refractory breast cancer who had been extensively treated previously, there were one complete and 11 partial responders, with an overall response rate of 40%. Six of the 12 patients who had previously received a conventional dose schedule of vinca alkaloids responded, including two who had progressed with intermittent bolus iv injections of vinblastine. Responses were seen in all organ sites of involvement, with durations of 2-8+ months (median, 6). Myelosuppression was mild to moderate at doses of between 1.4 and 1.8 mg/m2/day but became severe at 2 mg/m2, with leukopenia (wbcs, < 2000/mm3) and granulocytopenia (absolute granulocytes, < 1000/mm3) occurring in 75% of administered courses. Other toxic effects were infrequent and acceptable. Our results suggest that vinblastine given as a continuous 5-day infusion is highly effective in the treatment of patients with advanced metastatic breast cancer, including a few whose disease was felt to be resistant to a conventional dose schedule of vinca alkaloids.

Adult↗