Relationships in the structure-tissue distribution of basic drugs in the rabbit.
The relationship between the tissue-to-plasma partition coefficients (Kp) 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 (pKa) and lipophilicity were used. The Kp 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 (Kpfu) were calculated from Kpf (ratio of unbound drug). The true octanol-water partition coefficient of the nonionized drugs (P) was used to analyze the Kpf and Kpfu. In all tissues, log Kpfu was more highly correlated with log P than log Kpf.
Yokogawa
K
K
Hospital Pharmacy, Kanazawa University, Japan.
Nakashima
E
E
Ishizaki
J
J
Maeda
H
H
Nagano
T
T
Ichimura
F
F
D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D008055:Lipids / Q000032:analysis; D008297:Male; D008954:Models, Biological; D010599:Pharmacokinetics; D011817:Rabbits; D012995:Solubility; D013329:Structure-Activity Relationship; D014018:Tissue Distribution
D001798:Blood Proteins; D008055:Lipids