Pharmacokinetics of the analgesic o-carbamoylphenoxyacetic acid.

D Loew, O Schuster, G Menke, J Biehl

文献索引：Int. J. Clin. Pharmacol. Ther. Toxicol. 29(3) , 124-9, (1991)

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摘要

The pharmacokinetics of o-carbamoylphenoxyacetic acid was studied in 9 male healthy subjects following a single i.m. administration of 1000 mg of this compound in form of its sodium salt. Venous blood specimens were drawn up to the 10th h p.a. and the plasma concentration of o-carbamoylphenoxyacetic acid and its metabolite salicylamide were determined using a specific HPLC-assay. Following injection, o-carbamoylphenoxyacetic acid was rapidly distributed in the body since the maximal plasma concentration occurred within 0.37 +/- 0.08 h and was determined with 23.5 +/- 7.51 micrograms/ml in mean. In the following, the plasma concentration declined rapidly as well according to the mean terminal elimination half-life of 0.93 +/- 0.23 h. By contrast, plasma concentration of the metabolite salicylamide was comparatively low. Mean maximal plasma concentration amounted to only 0.18 +/- 0.03 microgram/ml and the peak concentration occurred 1.08 +/- 0.43 h after injection. The mean of the individual areas under the plasma concentration time profiles AUC(O-t) was 30.2 +/- 3.96 micrograms x h/ml for the parent compound and 0.69 +/- 0.14 microgram x h/ml for the metabolite. The relative mass portion of salicylamide vs o-carbamoylphenoxyacetic acid in systemic circulation was estimated with 0.008 comparing mean Cmax and with 0.023 comparing the mean areas AUC(O-t). A possible interpretation of these findings might be that a relatively stable ether bond exists in o-carbamoylphenoxyacetic acid which has to be cleaved during the formation of salicylamide. Due to the moderate rate of metabolic conversion, only minor quantities of salicylamide appeared in the systemic circulation. Furthermore, its peak concentration occurred at a time 2-3 times later than that of the parent compound.