title: Effects of water deprivation on the pharmacokinetics of DA-8159, a new erectogenic, in rats.
abstract: OBJECTIVE
  To test the effect of 72 h water deprivation on the non-renal clearance (CL) of DA-8159 in a rat model of dehydration. DA-8159 is mainly metabolized via CYP3A1/2 and the expression and mRNA level of CYP3A1/2 are not affected by dehydration.
  
  
  METHODS
  DA-8159 (30 mg/kg) was administered intravenously or orally to male control Sprague Dawley rats and rat model of dehydration.
  
  
  RESULTS
  As expected, after intravenous administration, the CL(NR) values of DA-8159 were comparable between two groups of rats. This could be supported by comparable intrinsic CL of DA-8159 using hepatic microsomes for both groups of rats. However, the CL was significantly slower in rat model of dehydration due, at least in part, to significantly slower renal CL in rat model of dehydration. The slower CL(R) in rat model of dehydration could be due to urine flow ratedependent renal CL of DA-8159; the less urine output, the less the urinary excretion of unchanged DA-8159. After oral administration, the AUC values of DA-8159 were not significantly different between two groups of rats, although the AUC of DA-8159 in rat model of dehydration was significantly greater than controls after intravenous administration. This could be possibly due to changes in the intestinal first-pass effects in rat model of dehydration.
  
  
  CONCLUSIONS
  After intravenous administration of DA-8159, the non-renal CL values were comparable between two groups of rats due to the lack of effect of dehydration on CYP3A1/2.
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, South Korea.
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Yu Chul
authors.initials: YC
authors.lastname: Kim
authors.forename: Myung Gull
authors.initials: MG
authors.lastname: Lee
authors.forename: Jong Won
authors.initials: JW
authors.lastname: Kwon
authors.forename: Moohi
authors.initials: M
authors.lastname: Yoo
mesh_terms: D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism*; D051544:Cytochrome P-450 CYP3A; D003681:Dehydration / Q000201:enzymology / Q000378:metabolism*; D007275:Injections, Intravenous; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000493:pharmacokinetics* / Q000494:pharmacology; D011743:Pyrimidines / Q000493:pharmacokinetics* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides; D014868:Water Deprivation; D000096926:Benzenesulfonamides
chemical_list: D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; D010726:Phosphodiesterase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; C465138:Cyp3a23-3a1 protein, rat; C419664:udenafil; D000096926:Benzenesulfonamides