651999 2,11616.7 1950 8510 200620201525205032.3 20013,00020293,379 10011,40010,000 6578.87574.9 6526.3656940.8 1994495 2,246 2 Vol. 22 No. 22000
Vol. 22 No. 22000 3
4 Vol. 22 No. 22000 1015 P450CYP CYP CYP3A CYP CYP3A
5 Vol. 22 No. 22000 pharmacokinetics pharmacodynamics 5-FU 7080 P450 P450 P450 P450 P4502030 P450 GOT P450 P450 CYP P450 CYP1A
Family Subfamily P450 CYP1 CYP1A CYP1A1 benzo[a]pyrene polycyclic aromatic hydrocarbons, cigarettes, omeprazole CYP1A2 13 caffeine, phenacetin, theophylline, taurine CYP2 CYP2A CYP2A6 CYP2A7 coumarin CYP2B CYP2B6 cyclophosphamide phenobarbital CYP2B7 CYP2C CYP2C8 tolbutamide rifampicin, phenobarbital CYP2C9 warfarin, NSAIDs, phenytoin mephenytoin, diazepam, 20 hexobarbital, R-mephobarbital, CYP2C19 omeprazole and other PPIs, proguanil, ethotoin CYP2D CYP2D6 2 metoprolol and other blockers, dextromethorphan, imipramine and other tricyclics, codeine, flecainide and other type IC antiarrhythmics, phenformin, sparteine, thioridazine, debrisoquine (total of ca. 30 drugs) CYP2E CYP2E1 7 ethanol, chlorzoxazone ethanol, isoniazid CYP3 CYP3A CYP3A3/4 CYP3A5 30 nifedipine and other dihydropyridines, ciclosporin, tacrolimus, testosterone, erythromycin and other macrolides, lidocaine, triazolam, quinidine, carbamazepine, terfenadine testosterone rifampicin, phenytoin, carbamazepine CYP4 CYP4B CYP4B1 testosterone clofibrate furafylline, enoxacin and some new quinolones, methoxalen, cimetidine sulfaphenazole, cimetidine omeprazole, cimetidine quinidine, fluoxetine, paroxetine, perphenazine, haloperidol, cimetidine chlormethizole, diehtyldithiocarbamate ketoconazole, itraconazole gestodene, diltiazem, verapamil, erythromycin, naringenin CYP1A1CYP1A2 P450 P450 P450 P450 6 Vol. 22 No. 22000
7 Vol. 22 No. 22000 P450 P450 40 1969 Hayton ergotism 20 N- P450 P450 P450 P450CYP3A P4503A33A43A53A7 3A7 CYP3A4 CYP3AP450 P450 1060 P450 CYP3A CYP3A CYP3A P450 P450 P450 P450 P450
P450 in vitrop450 P450 16 in vitrop450 P450 CYP3A CYP1A2 P450 P450mixed function oxidase P450 P450 P450 P450 CYP3ACYP2D6 P450 CYP3A P450 P450 P450 P450in vitro P450 8 Vol. 22 No. 22000
1998 Rowland M and Tozer TN : Clinical Pharmacokientics : Concept and Application, 3rd ed., Williams & Wilkins, Baltimore, 1995 Vol. 22 No. 22000 9
R DDSdrug delivery system DDS DDS DDS Vol. 22 No. 22000 11
12 Vol. 22 No. 22000
O/W W/O O/W W/O O/W O/W Vol. 22 No. 22000 13
O/W 14 Vol. 22 No. 22000
15 Vol. 22 No. 22000 ODT ODT ODT ODT ODT ODT ODT ODT ODT 40 1020 ODT ODTFU ODT McKenzie 100 2000 20 100
VI strongest 0.05 0.05 1,869 1,600 1,900 0.1 0.064 0.05 1,660 1,660 1,700 -DP very strong 0.1 0.05 0.1 0.1 0.1 0.05 220600 1,660 500 1,600 360 360 360 strong 0.12 0.025 0.12 0.3 0.025 360 500 100 360 360 V medium 0.1 0.02 0.1 0.05 0.1 75 361 50 360 A weak 0.1 0.25 0.5 43 17 0.5 Rook McKenzie and AtkinsonStoughton RB 1999 70 16 Vol. 22 No. 22000
MIC Dermatofile131995 Vol. 22 No. 22000 17
18 Vol. 22 No. 22000 FAPG 1/2
19 Vol. 22 No. 22000 PL O/W W/O 1981 1988 1992 1996 1999 1999 1091211281999 19suppl1997 391489 1496170517121997
ddddddddddddddddddddddddddddddddddddddddddddd ddddddddddddddddddddddddddddddddddddddddddddd Vol. 22 No. 22000 21
T TB 22 Vol. 22 No. 22000
Vol. 22 No. 22000 23
T T CD86T CD28CD86CD28 24 Vol. 22 No. 22000
T T deletion suppression anergy Vol. 22 No. 22000 25
T 26 Vol. 22 No. 22000
MHC MHC MHC HLA-GMHC Vol. 22 No. 22000 27
1875 24 1891 26 431968 14 28 Vol. 22 No. 22000
29 Vol. 22 No. 22000 1931 23
30 TTS1999 TTS10TTS20TTS3024 TTS30 TTS20TTS1010 TTS20 32 6.8 20.218.1 30 Vol. 22 No. 22000
TTS TTS 0120-77-0221 TTS 0120-37-7305 2071,000,000US$198Mio US$1998 Vol. 22 No. 22000 31
32 Vol. 22 No. 22000
karuophullon carophilum 16 1013 34 Vol. 22 No. 22000
12 1213 1497 Vasco da Gama14691524 1606 Amboina 1770 Mauritius1788 Penang Zanzibar Madagascar 60 18 60 756 1978 1848 1850 386534 502536659 Vol. 22 No. 22000 35
Clou Clove Eugenia Syzygium syzygos aromaticum CloveClou de Girofle GewürznelkenbaumGarofani Syzygium aromaticum Merrill et L. M. Perry 12m cm cm 1.3cm 2.5cm 1.2cm S. buxifolium Hook et Arn. S. cleyerifolium Makino Malabar plum, rose apple jambosier, pomme rose Jambos, Rosenaptel S.jambos (L.)Alston 12m 15 20cm 2.5cm Rhum de Pommerose Jambosin Iarge-fruited rose, Malay apple S. malaccense(l.)merrill et L. M. Perry 14m 20 30cm1014cm cm cm 36 Vol. 22 No. 22000
Black plum, jambolan, S. cuminii (L.) Skeels 13m 2.3cm 1319 rosewater apple jambo ayer wässeriger S. aqueum Alston 10m 1530cm cm 1619 Eugenol 7895 Acetly-eugenol -- Caryophyllene Vanillin Tannin 10Oleanolic acid 1.5 45 1993 g Vol. 22 No. 22000 37
171260 38 Vol. 22 No. 22000
100 1965 10 1970 NASAICAO 40 Vol. 22 No. 22000
41 Vol. 22 No. 22000 CRMCRM CRM B P E
42 Vol. 22 No. 22000 CRM PDSplan do see CRM
43 Vol. 22 No. 22000 CRM CRM CRM CRM
stop and look 44 Vol. 22 No. 22000
45 Vol. 22 No. 22000 stop and look 0.80.85880900 one thousand 15 2030 one thousasnd 1 1977 KLM
C3 KLM ATC KLM 400m we are at take off KLM 583 61 CRM 500 46 Vol. 22 No. 22000
47 Vol. 22 No. 22000 11
11101711 OTC Vol. 22 No. 22000 49
50 Vol. 22 No. 22000 40 ACE
51 Vol. 22 No. 22000 3050
52 Vol. 22 No. 22000 F 33
53 Vol. 22 No. 22000 10 PR
ADLQOL 54 Vol. 22 No. 22000
55 Vol. 22 No. 22000
56 Vol. 22 No. 22000
20 Vol. 22 No. 22000 57
59 Vol. 22 No. 22000 11111314 32 10 (1)(2) (1) (2) 10 11 14 16 17 18 21 24 27
1214301800 13 9301630 / / COPD/ 3F JR 1 03-3987-5078 FAX 03-3987-5647 1213 122013001600 1-6-17 103-3294-0271 FAX 03-3294-7359 FAX 1914001800 28FAX 1 03-3815-541135281 35282 FAX 03-3616-6159 191500 20 103-3785-3858FAX 03-3787-1325 121216 / // / SCS1-5-45 1-16-21 1-7-5 1-5- 45 WHO 103-5803-5190 FAX03-3818-7176 E-mailwhocc.hith@med.tmd.ac.jp WHO Vol. 22 No. 22000 61
159054 1594 24 50 159256 53 1591 18 57 1591 1595 1598 15 62 Vol. 22 No. 22000
18 62 17 700 Vol. 22 No. 22000 63
65 Vol. 22 No. 22000 8081 88 10 12 (1) (2) (1) (2) 2,000 2,000 51 52 82 82 82 12-001234
66 Vol. 22 No. 22000 12 13 10 1214 No.2 12 10 11 1211 1311 22 14 152000 16FAPA 1749 18117,940 11 ISDN 10 14 1650 18 22
67 Vol. 22 No. 22000 309 1112 11 22 11 0.8 12 22 11 12 29 11 14 10 27 1112 11 2000 4,400 500
68 Vol. 22 No. 22000 10 22389 300 101-0054 1 21 132940271 2,000 9025-53-1 12 JR10 JR10 JR P450
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