Quantitative Structure - Pharmacokinetic Relationships for Plasma Clearance of Basic Drugs with Consideration of the Major Elimination Pathway.

CONCLUSIONS: Plasma protein binding was the major restrictive factor for the CL of drugs, primarily cleared by metabolism.  The clearance was favored by lipophilicity and several structural features like OH-groups, aromatic rings, large hydrophobic centers, aliphatic groups, connected with electro-negative atoms, and non-substituted aromatic C-atoms. The presence of Cl-atoms and abundance of 6-member aromatic rings or fused rings had negative effect.  The presence of ether O-atoms contributed negatively to the CL of both metabolism and renally excreted drugs, and urine excretion was favored by the presence of 3-valence N-atoms. These findings give insight on the main structural features governing plasma CL of basic drugs and could serve as a guide for lead optimization in the drug development process. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page. PMID: 28554345 [PubMed - in process]
Source: Journal of Pharmacy and Pharmaceutical Sciences - Category: Drugs & Pharmacology Tags: J Pharm Pharm Sci Source Type: research