The relationship between the tissue-to-plasma partition coefficients (K(p)) and drug lipophilicity was investigated using highly lipophilic drugs with apparent partition coefficients of 150 or above in an octanol-water system at pH 7.4. Ten clinically popular basic drugs with different dissociation coefficients (pK(a)) and lipophilicity were used. The K(p) values were determined in nondisposing organs after the i.v. administration of individual drugs in rabbits. The free fraction in plasma and the blood-to-plasma concentration ratio were determined in vitro. Then the tissue-to-plasma ratios of nonionized and unbound drug concentrations (K(pfu)) were calculated from K(pf) (ratio of unbound drug). The true octanol-water partition coefficient of the nonionized drugs (P) was used to analyze the K(pf) and K(pfu). In all tissues, log K(pfu) was more highly correlated with log P than log K(pf).
ASJC Scopus subject areas
- Pharmaceutical Science