Distribution and metabolism of synthetic alkyl analogs of lysophosphatidylcholine in mice

Abstract

Stability, distribution and metabolic fate of alkyl analogs of lysophosphatidylcholine have been studied in mice. Analogs employed were 1-hexadecyl- and 1-dodecyl-propanediol-3-phosphorylcholine (2-deoxy-lysophosphatidylcholine) and rac-1-octadecyl-2-methyl-glycero-3-phosphorylcholine (2-methoxy-lysophosphatidylcholine). It is demonstrated that (1) the half-life of these compounds in the organism was increased to the order of days as compared to minutes or hours for natural lysophosphatidylcholine, (2) the analogs were slowly degraded in vivo with partial incorporation of the hydrophobic part into neutral lipids and phosphatidylcholine. Deoxy analogs were apparently degraded faster than methoxy derivatives, and (3) due to this metabolism, accumulation of these compounds, even after repeated injections, did not occur in mice. Intravenous and intraperitoneal injections led to rapid and complete distribution of the lysolipids with slight enrichment in liver, kidneys and intestine. Subcutaneous or oral application resulted in a similar distribution, however, remarkable depot effects at the sites of administration were observed. Experiments with tumor-bearing mice indicated a reduced metabolic turnover and thus a slight enrichment of ether-lysophosphatidylcholine analogs in tumor tissue.