title: [In vitro metabolism of forscolin isolated from Coleus forskohlii].
abstract: This paper is to report the study of the metabolism of forscolin in plasma and liver microsomes for guiding clinical therapy. Forscolin was quantified by HPLC-MS/MS. The metabolic stability of forscolin in rat, Beagle dog, monkey and human plasma and liver microsomes, mediated enzymes of forscolin and its inhibition on cytochrome P450 isoforms in human liver microsomes were studied. Results showed that forscolin was not metabolized in plasma of the four species but metabolized in liver microsomes of the four species. The t1/2 of forscolin in rat, Beagle dog, monkey and human liver microsomes were (52.0 +/- 15.0), (51.2 +/- 5.9), (6.0 +/- 0.2) and (11.9 +/- 1.8) min; CL(int) were (75.6 +/- 18.7), (60.9 +/- 6.8), (513.8 +/- 14.3) and (176.2 +/- 25.6) mL x min(-1) x kg(-1); CL were (34.8 +/- 4.5), (23.3 +/- 1.0), (40.3 +/- 0.5) and (17.9 +/- 0.3) mL x min(-1) x kg(-1), respectively. Forscolin was metabolized by CYP3A4 in human liver microsomes. There was definite inhibition on CYP3A4 at the concentrations of forscolin between 0.1 ng x mL(-1) and 5 microg x mL(-1). Therefore, forscolin is rapidly excreted from liver microsomes. Attention should be paid to the drug interaction when forscolin was used along with other drugs metabolized by CYP3A4 in clinics.
authors.affiliation: Pharmacy College of Central South University, Changsha 410013, China.
authors.forename: Man
authors.initials: M
authors.lastname: Zhang
authors.forename: Zhi-Yun
authors.initials: ZY
authors.lastname: Meng
authors.forename: Xiao-Xia
authors.initials: XX
authors.lastname: Zhu
authors.forename: Gui-Fang
authors.initials: GF
authors.lastname: Dou
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D031330:Coleus / Q000737:chemistry*; D005576:Colforsin / Q000097:blood / Q000302:isolation & purification / Q000378:metabolism*; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D004285:Dogs; D006801:Humans; D008251:Macaca; D008657:Metabolic Clearance Rate; D008862:Microsomes, Liver / Q000378:metabolism*; D010946:Plants, Medicinal / Q000737:chemistry; D051381:Rats; D053719:Tandem Mass Spectrometry
chemical_list: D005576:Colforsin; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human