Abstract
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 (p Ka) 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.
| Original language | English |
|---|---|
| Pages (from-to) | 691-696 |
| Number of pages | 6 |
| Journal | Pharmaceutical Research: An Official Journal of the American Association of Pharmaceutical Scientists |
| Volume | 7 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - 1990 Jul |
Keywords
- basic drugs
- distribution of nonionized drug
- lipophilicity
- pharmacokinetics
- rabbits
- tissue distribution
ASJC Scopus subject areas
- Biotechnology
- Molecular Medicine
- Pharmacology
- Pharmaceutical Science
- Organic Chemistry
- Pharmacology (medical)