Plasma and tissue binding as determinants of drug body distribution. Possible applications to toxicological studies.
1. Drugs are distributed through all body tissues via blood circulation. Consequently, most drugs rarely elicit one specific pharmacological effect but more generally have several, in different tissues. 2. In other words, drug effects are not unique or isolated, because drug distribution is not selective. Thus, considering a drug with a given liposolubility, its quantitative distribution in the body may be predicted in taking into account the physico-chemical properties of the compound and the blood flows and the lipid contents of the different tissues and organs it will reach. 3. This paper attempts to show that plasma binding can influence the tissue distribution of drugs and may be applied to the minimization of toxic effects by decreasing the amounts of drug reaching the relevant tissues. 4. The value of an early determination of drug binding in human blood will be emphasized. This is justified by the fact that tissue distribution of drugs does not vary greatly between species whereas plasma binding may show important inter-species differences. Thus different plasma binding in humans may lead to large variations in tissue distribution as compared with experimental animals.
Barre
J
J
Service Hospitalo-Universitaire de Pharmacologie, Faculté de Médecine de Paris XII, France.
Urien
S
S
Albengres
E
E
Tillement
J P
JP
D000818:Animals; D006801:Humans; D050356:Lipid Metabolism; D004364:Pharmaceutical Preparations / Q000097:blood; D010599:Pharmacokinetics; D011485:Protein Binding; D014018:Tissue Distribution; D014116:Toxicology / Q000379:methods
D004364:Pharmaceutical Preparations