Correlation of physicochemical properties with absorption and metabolism of some tricyclic drugs.
Octanol and dodecane partition coefficients, surface activity and adsorbability to activated charcoal were determined for six tricyclic psychotropic drugs with N-dimethylalkyl side chains. Surface activity correlated well with the partition coefficients, and all drugs obeyed the Langmuir adsorption isotherm. A correlation between the reciprocal of the death time of gold fish exposed to drugs and partition coefficients was observed. The extent to which the drugs were N-demethylated as measured by formaldehyde formed in rat liver homogenate incubations correlated with their adsorbability to activated charcoal but not with their ability to inhibit aniline-p-hydroxylase, nor was there a linear correspondence between N-DEMETHYLATION AND DRUG LIPOPHILICITY AS INDICATed by partition coefficients or surface activity.
D000042:Absorption; D000639:Amitriptyline; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000378:metabolism; D002746:Chlorpromazine; D004316:Doxepin; D007099:Imipramine; D066298:In Vitro Techniques; D008297:Male; D008745:Methylation; D010640:Phenothiazines / Q000378:metabolism; D011395:Promazine; D011398:Promethazine; D051381:Rats; D013500:Surface Tension
D000929:Antidepressive Agents, Tricyclic; D010640:Phenothiazines; D004316:Doxepin; D000639:Amitriptyline; D011398:Promethazine; D011395:Promazine; D007099:Imipramine; D002746:Chlorpromazine