Alterations of Gefitinib Pharmacokinetics by Co-administration of Herbal Medications in Rats / 中国结合医学杂志

<p><b>OBJECTIVE</b>To evaluate the potential pharmacokinetic interactions of the anticancer agent gefitinib (Iressa®) and the oriental medications Guipi Decoction (, GPD, Guibi-tang in Korean) and Bawu Decoction (, BWD, Palmul-tang in Korean).</p><p><b>METHODS</b>Methylcellulose (MC, control), GPD (1,200 mg/kg), or BWD (6,000 mg/kg) was orally administered to rats either as a single dose or multiple doses prior to gefitinib administration. To examine the effects of a single dose of the herbal medicines, gefitinib (10 mg/kg) was orally administered after 5 min or 1 h of MC or the herbal medicine pretreatments. To examine the effects of the multiple doses of the herbal medicines, gefitinib (10 mg/kg) was orally administered following 7 consecutive days of the administration of MC or each herbal medicine. The plasma concentrations of gefitinib were determined with liquid chromatography-tandem mass spectrometry assay. The plasma concentration-time profiles of gefitinib were analyzed with a noncompartmental analysis.</p><p><b>RESULTS</b>Gefitinib was rapidly absorbed and showed a monoexponential decline with an elimination half-life of 3.7-4.1 h. The pharmacokinetics of gefitinib was not affected by GPD pretreatment. However, a significantly lower maximum plasma concentration (C, P<0.05) and area under the curve (P<0.05), and a delayed time to reach C (T, P<0.01) were observed in both single- and multipledose BWD-pretreated rats compared with the control rats.</p><p><b>CONCLUSIONS</b>BWD and not GPD might delay and interfere with gefitinib absorption. Further evaluations of the clinical significance of these findings are needed.</p>

Cytotoxic Triterpenoids from the Fruits of Ligustrum japonicum

Medicinal plants are potential sources of anticancer agents screening. A large number of phytochemicals, including triterpenoids, have been reported to have significant cytotoxic effects on cancer cells. From the fruits of Ligustrum japonicum Thunb., thirteen triterpenoids (1 – 13) were isolated and evaluated for their cytotoxic activity against Hela and HL-60 cells. As results, 8 (oleanolic acid) showed significant effects on Hela with IC50 values of 5.5 µM, and moderate effects on HL-60 cells with IC₅₀ values of 55.9 µM. Meanwhile, 10 (oleanderic acid) and 11 (3β-acetoxy-urs-12-en-28-oic acid) exhibited moderate inhibitory effects on Hela with IC₅₀ value of 55.0 and 68.8 µM, respectively. Moreover, 10 showed cytotoxic effect on HL-60 cell line with IC₅₀ value of 63.9 µM. To our knowledge, this is the first report that oleanderic acid was isolated from L. japonicum and investigated in cytotoxic effects on Hela and HL-60 cells.