title: Relationship between lipophilicity and absorption from the liver surface of paraben derivatives and antipyrine in rats.
abstract: OBJECTIVE
  The importance of drug lipophilicity on absorption from the liver surface was examined in rats using paraben derivatives, antipyrine, Sudan III, and Sudan blue.
  
  
  METHODS
  The log partition coefficient (PC) of n-octanol/water ranged from -1.39 to 4.62. The compounds were applied to the rat liver surface using a cylindrical diffusion cell (i.d. 9 mm).
  
  
  RESULTS
  The rate of absorption at 15 min was calculated to be 13.9% for paraben, much lower than that for its derivatives methylparaben, propylparaben and butylparaben (∼ 80%). The obtained first-order absorption rate constant (k(a) ) of paraben, methylparaben, propylparaben and antipyrine increased according to lipophilicity. Further lipophilicity resulted in a fall in k(a) , implying the importance of affinity for lipids and water in absorption from the liver surface. Thus, a compound with a log PC of around 2.5 is considered to have maximum absorbability from the rat liver surface. A good relationship (r(2) = 0.97) was recognized between the log k(a) and log reciprocal value with the square root of molecular weight of the compounds with a log PC below 2.5.
  
  
  CONCLUSIONS
  The rate of absorption of a drug from the liver surface could be estimated from physicochemical properties such as lipophilicity and molecular weight.
authors.affiliation: Department of Clinical Pharmacy, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan. koyo-n@nagasaki-u.ac.jp
authors.forename: Koyo
authors.initials: K
authors.lastname: Nishida
authors.forename: Masanori
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Miyamoto
authors.forename: Naoki
authors.initials: N
authors.lastname: Yoshikawa
authors.forename: Shintaro
authors.initials: S
authors.lastname: Fumoto
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sasaki
authors.forename: Junzo
authors.initials: J
authors.lastname: Nakamura
mesh_terms: D000818:Animals; D000983:Antipyrine / Q000737:chemistry / Q000378:metabolism*; D001692:Biological Transport; D008055:Lipids / Q000737:chemistry*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008970:Molecular Weight; D010226:Parabens / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013499:Surface Properties
chemical_list: D008055:Lipids; D010226:Parabens; D000983:Antipyrine