Pharmacokinetics of coumarin, 7-hydroxycoumarin and 7-hydroxycoumarin glucuronide in the blood and brain of gerbils following intraperitoneal administration of coumarin.
Blood and brain concentration-time profiles were obtained in gerbils following intraperitoneal administration of coumarin (C). The data were fit to one- or two-compartment models using several computer programs including NONLIN, modified ESTRIP, RESID and AUC-RPP. The data indicate that coumarin distributes rapidly into the brain tissue reaching about one half the blood concentration at peak time. The peak time brain coumarin concentration and subsequent rapid removal from brain correlates well with the transient sedative effect of coumarin. Area under the curve estimations indicate that 7-hydroxycoumarin and 7-hydroxycoumarin glucuronide distribute into brain tissue to a negligible extent if at all. The pharmacokinetic profile of C as well as the metabolic 7-hydroxylation and glucuronidation found in the blood of the gerbil is similar to that found in man. This would suggest that the gerbil is potentially a good model for pharmacokinetic and pharmacological investigations of C for correlation with human studies.
D000818:Animals; D001921:Brain / Q000378:metabolism*; D003374:Coumarins / Q000097:blood / Q000378:metabolism*; D004929:Esculin / Q000378:metabolism*; D005419:Flavonoids / Q000378:metabolism*; D005849:Gerbillinae; D007274:Injections, Intraperitoneal; D007700:Kinetics; D008297:Male; D014468:Umbelliferones / Q000097:blood / Q000378:metabolism*
D003374:Coumarins; D005419:Flavonoids; D014468:Umbelliferones; D004929:Esculin; C031477:7-hydroxycoumarin; C030123:coumarin