Nedaplatin

Nedaplatin is a derivative of cisplatin and DNA damage agent.Target: OthersNedaplatin(NDP) is a derivative of cisplatin which produced less nausea & vomiting and nephrotoxicity. the effect of NDP on the 7-ethyl-1-hydroxy-CPT (the active form of CPT-11)-induced inhibitory effect on DNA topoisomerase I was examined. The topoisomerase I-inhibitory effect of 7-ethyl-1-hydroxy-CPT was enhanced 10-fold in the presence of NDP at microgram/milliliter concentrations [1]. NDP was developed as a second generation platinum complex. Because it has greater antitumour activity and lower nephrotoxicity than cisplatin (CDDP). At the high-dose of NDP in FN therapy, a reduction of tumour size and long-term tumour-free survival were frequently observed. The survival effect of the combinations of NDP with 5-FU was superior to those of the combination of CDDP with 5-FU. In conclusion, the sequence-dependent antitumour efficacy and toxicity of the combination of NDP or CDDP with 5-FU was demonstrated in this study, and FN therapy appeared to be the most efficient regimen as a clinical therapy [2].

Signaling Pathways >> Cell Cycle/DNA Damage >> DNA/RNA Synthesis

Research Areas >> Cancer

[1]. Kanzawa, F., et al., In vitro synergistic interactions between the cisplatin analogue nedaplatin and the DNA topoisomerase I inhibitor irinotecan and the mechanism of this interaction. Clin Cancer Res, 2001. 7(1): p. 202-9.

[2]. Uchida, N., et al., Sequence-dependent antitumour efficacy of combination chemotherapy of nedaplatin, a novel platinum complex, with 5-fluorouracil in an in vivo murine tumour model. Eur J Cancer, 1998. 34(11): p. 1796-801.

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MOLECULAR FORMULA :

C2-H8-N2-O3-Pt

MOLECULAR WEIGHT :

303.21

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

20 mg/kg

TOXIC EFFECTS :

Kidney, Ureter, Bladder - changes in tubules (including acute renal failure, acute tubular necrosis) Kidney, Ureter, Bladder - other changes in urine composition Nutritional and Gross Metabolic - changes in sodium

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

44100 ug/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

4 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

48600 ug/kg/26W-I

TOXIC EFFECTS :

Cardiac - other changes Kidney, Ureter, Bladder - other changes Endocrine - other changes

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

10800 ug/kg/26W-I

TOXIC EFFECTS :

Kidney, Ureter, Bladder - changes in bladder weight Blood - changes in platelet count Related to Chronic Data - changes in testicular weight

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - guinea pig

DOSE/DURATION :

45 mg/kg/30D-I

TOXIC EFFECTS :

Sense Organs and Special Senses (Ear) - change in acuity Sense Organs and Special Senses (Ear) - changes in cochlear structure or function

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

DOSE :

13 mg/kg

SEX/DURATION :

female 17-21 day(s) after conception lactating female 20 day(s) post-birth

TOXIC EFFECTS :

Reproductive - Maternal Effects - other effects Reproductive - Effects on Newborn - physical Related to Chronic Data - changes in ovarian weight

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

DOSE :

4500 ug/kg

SEX/DURATION :

female 17-21 day(s) after conception lactating female 20 day(s) post-birth

TOXIC EFFECTS :

Reproductive - Effects on Newborn - physical

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

DOSE :

46 mg/kg

SEX/DURATION :

male 64 day(s) pre-mating female 2 week(s) pre-mating - 7 day(s) after conception

TOXIC EFFECTS :

Reproductive - Paternal Effects - other effects on male Reproductive - Maternal Effects - menstrual cycle changes or disorders Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

DOSE :

46 mg/kg

SEX/DURATION :

male 64 day(s) pre-mating female 2 week(s) pre-mating - 7 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Effects on Embryo or Fetus - fetal death

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

DOSE :

750 mg/kg

SEX/DURATION :

female 7 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Specific Developmental Abnormalities - musculoskeletal system

MUTATION DATA

TEST SYSTEM :

Rodent - mouse

DOSE/DURATION :

6300 ug/kg

REFERENCE :

IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 22,821,1991