Relationship between lipophilicity and protein binding of a homologous series of barbiturates

Chen Hsi Chou, Malcolm Rowland

Research output: Contribution to journalArticlepeer-review


The relationship between lipophilicity and protein binding of drugs was elucidated for a homologous series of 5-n-alkyl-5-ethyl barbituric acids (hexyl, heptyl, octyl, nonyl) with LogP (octanol-water partition coefficient) of 3.08 or above. The binding of these four lipophilic barbituric acids to human serum albumin (HSA) was determined using equilibrium dialysis. The barbiturates (10 mg/L)/HSA solution was dialyzed against Krebs-Henseleit bicarbonate buffer (pH 7.4) at 37°C for 7 hr, by which time equilibrium was established. No significant volume shift or non-specific adsorption occurred and barbiturates were stable during the dialysis period. The extent of binding increased with increasing length of the alkyl chain, and for all barbiturates the unbound fraction decreased as the concentration of HSA increased from 0.05 to 4 %. The relationship between unbound fraction of barbiturates and concentration of HSA can be described by a single binding site model. The apparent association binding constants (KA) estimated for hexyl, heptyl, octyl and nonyl homologs were 4.8, 21, 66 and 101 × 103 M-1, respectively. A linear relationship was found when LogKA was plotted against LogP, the index of lipophilicity. These results indicate that these homologous barbiturates have high affinities to HSA, and that binding of these barbiturates is primarily determined by lipophilicity.

Original languageEnglish
Pages (from-to)87-94
Number of pages8
JournalChinese Pharmaceutical Journal
Issue number2
Publication statusPublished - 2002

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science


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