Abstract:
:The in vitro antitumor activity of navelbine (NVB, KW-2307), a newly synthesized vinca alkaloid, was compared with that of adriamycin (ADM) against human breast carcinomas inoculated into nude mice at the maximum tolerated dose (MTD) and clinically equivalent dose (CED). The plasma levels of NVB after intravenous injection into nude mice at doses of 1.2 and 4.8 mg/kg diminished rapidly during the early phase (0-1 h), followed by a very long shallow one. NVB was still detected 96 h after administration at a dose of 4.8 mg/kg. The pharmacokinetic parameters of NVB in plasma indicated that NVB extensively distributes to tissues. The CED of NVB was provisionally decided to be 4.8 mg/kg based on the comparison of AUC values at 24-infinity h between human patients and nude mice. When compared by a single injection of MTD (NVB, 16 mg/kg; ADM 12 mg/kg), NVB was effective against all four tumor lines, MC-2, MC-8, MMKY and H-31, while ADM was effective only against H-31. On the other hand, the body weight loss by NVB was mild as compared with that by ADM, indicating that the antitumor activity of NVB is superior to that of ADM at their MTDs. A single injection of NVB at its CED (4.8 mg/kg) produced a poor antitumor effect and no or little toxicity in terms of body weight loss, as compared with those at MTD. However, when NVB was administered intermittently at CED, it exhibited significant antitumor activity against three tumor lines. The body weight loss was still mild even on this intermittent schedule.(ABSTRACT TRUNCATED AT 250 WORDS)
journal_name
Anticancer Drugsjournal_title
Anti-cancer drugsauthors
Tsuruo T,Inaba M,Tashiro T,Yamori T,Ohnishi Y,Ashizawa T,Sakai T,Kobayashi S,Gomi Kdoi
10.1097/00001813-199412000-00004subject
Has Abstractpub_date
1994-12-01 00:00:00pages
634-40issue
6eissn
0959-4973issn
1473-5741journal_volume
5pub_type
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