PMID- 16028105
OWN - NLM
STAT- MEDLINE
DCOM- 20051223
LR  - 20141120
IS  - 0344-5704 (Print)
IS  - 0344-5704 (Linking)
VI  - 57
IP  - 1
DP  - 2006 Jan
TI  - Study on brain targeting of raltitrexed following intranasal administration in 
      rats.
PG  - 97-104
AB  - PURPOSE: To investigate the levels of raltitrexed (RTX) in blood and different 
      brain tissues in rats and to find out whether there is any direct drug transport 
      from nasal cavity to brain tissues following intranasal (i.n.) administration. 
      METHODS: Raltitrexed was administered to male Sprague-Dawley rats either 
      intranasally or intravenously. Drug concentrations in blood and brain tissues 
      were determined at different times post dosing. RESULTS: The plasma levels 
      achieved after i.n. administration were significantly lower than those following 
      intravenous (i.v.) administration (P < 0.05) before 120 min; but were 
      significantly higher (P < 0.05) after 120 min. Following i.n. administration, RTX 
      concentrations in different brain tissues were constantly detected for quite a 
      long time and differed significantly from each other, the rank order being C (OB) 
      > C (OT) > C (CR) > C (CL). On the contrary, RTX appeared only at the initial two 
      or three time points in different brain regions after i.v. injection, and the 
      concentrations were similar. AUC values in four brain regions by the nasal route 
      were 54- to 121-fold compared with the i.v. route, the drug targeting index (DTI) 
      values of nasal route were 71-158 for different brain regions, and about 99% of 
      RTX content within 360 min in the brain were transported via the olfactory 
      pathway. CONCLUSIONS: These results showed that antineoplastic RTX could be 
      directly transported into the brain via the olfactory pathway in rats.
FAU - Wang, Dongxing
AU  - Wang D
AD  - Beijing Institute of Pharmacology and Toxicology, Haidian District, Beijing, 
      10085, People's Republic of China.
FAU - Gao, Yongliang
AU  - Gao Y
FAU - Yun, Liuhong
AU  - Yun L
LA  - eng
PT  - Journal Article
DEP - 20051105
PL  - Germany
TA  - Cancer Chemother Pharmacol
JT  - Cancer chemotherapy and pharmacology
JID - 7806519
RN  - 0 (Antimetabolites, Antineoplastic)
RN  - 0 (Quinazolines)
RN  - 0 (Thiophenes)
RN  - FCB9EGG971 (raltitrexed)
SB  - IM
MH  - Administration, Intranasal
MH  - Animals
MH  - Antimetabolites, Antineoplastic/blood/*pharmacokinetics
MH  - Area Under Curve
MH  - Biological Availability
MH  - Brain/*metabolism
MH  - Injections, Intravenous
MH  - Male
MH  - Quinazolines/blood/*pharmacokinetics
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Thiophenes/blood/*pharmacokinetics
MH  - Tissue Distribution
EDAT- 2005/07/20 09:00
MHDA- 2005/12/24 09:00
CRDT- 2005/07/20 09:00
PHST- 2004/12/02 00:00 [received]
PHST- 2005/02/25 00:00 [accepted]
PHST- 2005/07/20 09:00 [pubmed]
PHST- 2005/12/24 09:00 [medline]
PHST- 2005/07/20 09:00 [entrez]
AID - 10.1007/s00280-005-0018-3 [doi]
PST - ppublish
SO  - Cancer Chemother Pharmacol. 2006 Jan;57(1):97-104. doi: 
      10.1007/s00280-005-0018-3. Epub 2005 Nov 5.