Development of predictive retention-activity relationship models of tricyclic antidepressants by micellar liquid chromatography.
The distribution of tricyclic antidepressants from plasma to brain, where these drugs exert their main clinical action, and other organs is related to transport events across the cell membranes of the different tissues. It could be expected that all the molecular features that condition the transport processes (mainly hydrophobicity and molar total charge) also control the pharmacokinetic and biochemical behavior. Micellar liquid chromatography (MLC) has been proposed to emulate in vitro the partitioning process in the biomembranes. The use of micellar solutions of Brij35 as mobile phases in reversed-phase liquid chromatography has proven to be valid to predict the biological activities of local anesthetics, barbiturates, catecholamines, and benzodiazepines. In this paper, the relationships between the capacity factor in MLC and some pharmacokinetic parameters and biological responses of tricyclic antidepressants are studied. Predictive regression models for the estimation of these parameter values, using the logarithm of the retention data (log k) as independent variable, are also proposed.
Quiñones-Torrelo
C
C
Departamento de Química Analítica, Universidad de Valencia, C/Vicente Andrés Estellés s/n, E-46100 Burjassot, Valencia, Spain.
Sagrado
S
S
Villanueva-Camañas
R M
RM
Medina-Hernández
M J
MJ
D000067956:Adenylyl Cyclase Inhibitors; D000317:Adrenergic alpha-Antagonists / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D002853:Chromatography, Liquid; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D008823:Micelles; D008954:Models, Biological; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000067956:Adenylyl Cyclase Inhibitors; D000317:Adrenergic alpha-Antagonists; D000929:Antidepressive Agents, Tricyclic; D004791:Enzyme Inhibitors; D006634:Histamine H1 Antagonists; D008823:Micelles; D009638:Norepinephrine; D018340:Receptors, Adrenergic, alpha-1; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors