| Project/Area Number |
11672268
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | Miyazaki Medical College |
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Principal Investigator |
ARIMORI Kazuhiko Miyazaki Medical College, Pharmacy, Professor, 医学部, 教授 (70253739)
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| Co-Investigator(Kenkyū-buntansha) |
NAKANO Masahiro Kumamoto University Hospital, Pharmacy, Professor, 医学部・附属病院, 教授 (40002125)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2000: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1999: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | protease inhibitor / therapeutic drug monitoring / nelfinavir / ritonavir / saquinavir / phenytoin / p-glycoprotein / AIDS / 相互作用 / L-MDR1細胞 / ブロモクリプチン |
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| Research Abstract |
The aim of the present study was to elucidate the factors on variations in serum levels of protease inhibitors in human immunodeficiency virus (HIV) infected patients. We determined the serum levels of two protease inhibitors, nelfinavir and saquinavir, in HIV infected patients who took many kinds of drugs. There was great individual variation in the serum levels of the protease inhibitors, probably due to the interaction with co-administered drugs or hepatic dysfunction. In a case of a patient taking phenytoin and nelfinavir, the reduced nelfinavir levels in the serum was attributed to the induction of cytochrome P-450- 3A .
The interaction of HIV protease inhibitors and HIV reverse transcriptase inhibitors was investigated in in-vitro study using L-MDR1 and L-mdr1a cell line, P- glycoprotein (P-gp) overexpressing cell. It was confirmed that saquinavir, ritonavir and nelfinavir were all a substrate for P-gp. Nelfinavir and ritonavir also were an inhibitor for P-gp, whereas other protease inhibitors (saquinavir, indinavir and amprenavir) and five nucleoside reverse transcriptase inhibitors (zidovudine, didanosine, zalcitabine, stavudine and lamivudine) were not. Ritonavir and saquinavir slightly inhibited the function of MRP which is an efflux-transporter as well as P-gp. These results provide useful informations for the treatment of HIV infected patients receiving a combination therapy of protease inhibitors.
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