Rapid determination of partition coefficients between n-octanol/water for cardiovascular therapies.
The lipid solubility of a pharmaceutical may greatly influence its tissue activity. To evaluate lipid solubility of a group of cardiovascular agents a procedure to determine partition coefficients in n-octanol/water for a series of cardiovascular compounds was described. Ultraviolet absorbance measurements were used to assess partitioning between the two liquid phases of these compounds. In this study, sotalol was found to be the most hydrophilic (n-octanol/water ratio of 0.33) and fosinopril-sodium was the most lipophilic (ratio of 6.19). This is a versatile method permitting the evaluation of lipophilicity and, thus, parameters governing the events leading to pharmacologic actions such as gastrointestinal dissolution, absorption, and bioavailability. These observations can be related to a drug series, composed of several compounds having structural similarities or minor variations. The lipid solubility of a compound can markedly alter its side-effects profile, especially because lipophilic drugs enter the central nervous system with facility. Additionally, lipophilic agents may enter target tissue with greater ease than nonlipophilic compounds and thus possess local intracellular effects in addition to a macro systemic action.
Ranade
Vasant
V
Department of Clinical Pharmacology, Rush University, Chicago, IL, USA.
Somberg
John C
JC
D020003:1-Octanol / Q000737:chemistry*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000737:chemistry; D000889:Anti-Arrhythmia Agents / Q000737:chemistry; D000959:Antihypertensive Agents / Q000737:chemistry; D002317:Cardiovascular Agents / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007202:Indicators and Reagents; D012995:Solubility; D012997:Solvents / Q000737:chemistry*; D014867:Water
D000806:Angiotensin-Converting Enzyme Inhibitors; D000889:Anti-Arrhythmia Agents; D000959:Antihypertensive Agents; D002317:Cardiovascular Agents; D007202:Indicators and Reagents; D012997:Solvents; D014867:Water; D020003:1-Octanol