PMID- 23517541
OWN - NLM
STAT- MEDLINE
DCOM- 20140602
LR  - 20130910
IS  - 1366-5928 (Electronic)
IS  - 0049-8254 (Linking)
VI  - 43
IP  - 10
DP  - 2013 Oct
TI  - Comparative pharmacokinetics of N(omega)-hydroxy-nor-L-arginine, an arginase 
      inhibitor, after single-dose intravenous, intraperitoneal and intratracheal 
      administration to brown Norway rats.
PG  - 886-94
LID - 10.3109/00498254.2013.780672 [doi]
AB  - 1.  Rodent studies have documented that N(omega)-hydroxy-nor-L-arginine (nor-NOHA), 
      an arginase inhibitor, has therapeutic potential in the treatment of 
      cardiovascular and obstructive airway diseases. However, its bioavailability and 
      pharmacokinetics have not been described so far. 2.  Anesthetized brown Norway 
      rats were administered single doses of nor-NOHA (10, 30 or 90 mg/kg) 
      intravenously (i.v.), intraperitonealy (i.p.) or via intratracheal (i.t.) 
      instillation of aerosol. Plasma nor-NOHA was assayed using a validated HPLC 
      method. 3.  Upon i.v. administration, the mean concentration showed a biphasic 
      decline and its value dropped below 10% of the maximum after 20 min. The 
      pharmacokinetics were linear with the total and inter-compartmental clearances of 
      33 and 17 mL/min/kg, central and peripheral volumes of distribution of 0.19 and 
      0.43 L/kg and terminal half-life of 30 min. 4.  The average absolute 
      bioavailability of nor-NOHA after i.p. and i.t. delivery was 98% and 53%, 
      respectively. The absorption from the airways was rate-limiting and its extent 
      decreased with the dose. 5.  In conclusion, nor-NOHA is rapidly cleared from the 
      plasma in concordance with the short time window of its in vivo inhibitory 
      activity reported in the literature. I.t. instillation of aerosol for topical 
      effects of nor-NOHA in the airways is characterized with significant systemic 
      availability.
FAU - Havlinova, Zuzana
AU  - Havlinova Z
AD  - Department of Pharmacology and.
FAU - Babicova, Andrea
AU  - Babicova A
FAU - Hroch, Milos
AU  - Hroch M
FAU - Chladek, Jaroslav
AU  - Chladek J
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130321
PL  - England
TA  - Xenobiotica
JT  - Xenobiotica; the fate of foreign compounds in biological systems
JID - 1306665
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (N(omega)-hydroxynorarginine)
RN  - 94ZLA3W45F (Arginine)
RN  - EC 3.5.3.1 (Arginase)
SB  - IM
MH  - Administration, Intravenous
MH  - Animals
MH  - Arginase/*antagonists & inhibitors
MH  - Arginine/administration & dosage/*analogs & derivatives/blood/pharmacokinetics
MH  - Biological Availability
MH  - Drug Administration Routes
MH  - Enzyme Inhibitors/administration & dosage/blood/pharmacokinetics
MH  - Half-Life
MH  - Injections, Intraperitoneal
MH  - Male
MH  - Models, Theoretical
MH  - Rats
EDAT- 2013/03/23 06:00
MHDA- 2014/06/03 06:00
CRDT- 2013/03/23 06:00
PHST- 2013/03/23 06:00 [entrez]
PHST- 2013/03/23 06:00 [pubmed]
PHST- 2014/06/03 06:00 [medline]
AID - 10.3109/00498254.2013.780672 [doi]
PST - ppublish
SO  - Xenobiotica. 2013 Oct;43(10):886-94. doi: 10.3109/00498254.2013.780672. Epub 2013 
      Mar 21.