2.7 2.7.5 1) 199846410-437 2) UTI ( )UTI ( 3 )Chemotherapy (Tokyo) 1986 34408-441 3) () 199745762-778 4) 1992 5) 199543 6) Chemotherapy (Tokyo) 199139687-689 7) Imipenem/Cilastatin sodium (MK-0787/MK-0791) Chemotherapy (Tokyo) 198533: 825-833 8) Meropenem Chemotherapy (Tokyo) 1992; 40620-630 9) Meropenem Chemotherapy (Tokyo) 1992 ; 40646-650. 10) Imipenem/Cilastatin sodium (MK- 0787/MK-0791) Chemotherapy (Tokyo) 1985331046-1063. 11) Panipenem/Betamipron Jpn J antibiotics 199245155-159. 12) Meropenem Jpn J Antibiotics 199345159-163. 13) Panipenem/betamipron (CS-976) 19923837-55 14) Meropenem Chemotherapy (Tokyo) 199240 710-718 15) Panipenem/Betamipron Jpn J Antibiotics 199245197-207 16) Meropenem Chemotherapy (Tokyo) 199240751-754 17) panipenem/betamipron Chemotherapy (Tokyo) 199139666-
2.7 672 18) Meropenem Chemotherapy (Tokyo) 199240689-700 19) panipenem/betamipron Chemotherapy (Tokyo) 199139 647-664 20) Meropenem Chemotherapy (Tokyo) 199240732-745 21) Meropenem Chemotherapy (Tokyo) 199240500-506 22) Imipenem/Cilastatin sodium (MK-0787/MK-0791) Chemotherapy (Tokyo) 198533942-949 23) MK-0787/MK-0791 Piperacillin 198660345-377 24) panipenem/betamipron imipenem/cilastatin Chemotherapy (Tokyo) 199240613-637 25) panipenem/betamipron imipenem/cilastatin Chemotherapy (Tokyo) 1992 40509-531 26) meropenem imipenem/cilastatin sodium Chemotherapy (Tokyo) 1992401426-1450 27) meropenem imipenem/cilastatin sodium Chemotherapy (Tokyo) 1992401343-1364 28) biapenem imipenem/cilastatin 19954363-84 29) biapenem imipenem/cilastatin 1995 4341-62 30) biapenem imipenem/cilastatin 20004845-67 31) 2) 1996112-123
2.7 32) 1) 1996180-190 33) UTI ( )UTI ( 3 ) Chemotherapy (Tokyo) 199139894-933 34) Meropenem 199238496-508 35) Meropenem 199238524-537 36) 19981795-122 37) Knaus WA, Draper EA, Wagner DP, Zimmerman JEAPACHEA severity of disease classification systemcritical Care Medicine 198513818-829 38) Cometta A, Baumgartner JD, Lew D, Zimmerli W, Pittet D, Chopart P et alprospective randomized comparison of imipenem monotherapy with imipenem plus netilmicin for treatment of severe infections in nonneutropenic patientsantimicrob Agents Chemother 1994June 1309-1313 39) Beaucaire GClinical activity of cefepime in severe infectionsclin Microbiol Infect 19995 S6-S14 40) M.P.Fink, D.R.Snydman, M.S.Niderman, K.V.Leeper,Jr., R.H.Johnson, S.O.Heard et al. Treatment of severe pneumonia in hospitalized patients: Results of a multicenter, randomized, double-blind trial comparing intravenous ciprofloxacin with imipenem-cilastatin. Antimicrob. Agents Chemother. 199438547-557 41) F.A.Lerma, on behalf of the serious infection study group. Efficacy of meropenem as monotherapy in the treatment of ventilator-associated pneumonia. J. Chemother. 2001 ; 13 :70-81 42) 2002
Report122.7 2.7.6 2.7.6-1 ( 1) R1411 10 25 mg 50 mg125 mg 250 mg500 mg R1412 24 125 mg 250 mg500 mg 1000 mg R1414 8 500 mg 1 2 R1417 8 1000 mg 1 2 R1419 500 mg 3 6 500 mg 1 3 Report04 1 19 5.3.3-19 Report01 1 19 19 6 (11 ) 6 (11 ) 1 (3 ) 5.3.3- Report02 1 19 5.3.3- Report03 1 19 19 5.3.3-1 20 5.3.3- Report05 R142G R142H R143P R143Q R143S ( ) ( ) ( ) ( ) ( ) ( ) ( ) R143T R143V R143W ( ) 14 250 mg500 mg 13 250 mg 11 250 mg 12 250 mg 10 250 mg 5 250 mg 10 250 mg 5 250 mg 4 19 19 1 19 19 5 4 20 20 20 20 1 20 20 1 20 20 5.3.3- Report06 5.3.3- Report07 5.3.3- Report08 5.3.3- Report09 5.3.3- Report10 5.3.3- Report11 2 20 20 1 20 5.3.3-20 5.3.3- Report13
2.7 2.7.6-1 ( 2) Report03Report06 R1415 R1418 R1416 R142R R142U R143R R143U R142A R142C ( ) ( ) R142D ( ) 6 250 mg 12 250 mg 8 250 mg 83 250 mg500 mg 1 2 83 250 mg500 mg 1 2 219 250 mg 1 2 (MEPM) 500 mg 1 2 205 250 mg 1 2 (MEPM) 500 mg 1 2 1 20 5.3.3- Report14 1 20 20 1 1 20 20 14 107 125 mg 1 2 3 250 mg 1 2 14 250 mg 1 3 500 mg 1 2 114 3 250 mg 1 2 250 mg 1 3 500 mg 1 2 45 250 mg 1 2 250 mg 1 3 500 mg 1 2 30 5 32 7 56 5 42 14 3 14 41 55 27 19 19 19 19 20 20 20 20 19 19 19 19 19 19 5.3.3- Report15 5.3.3- Report16 5.3.5- Report01 5.3.5- Report02 5.3.5-5.3.5- Report04 5.3.5- Report05 5.3.5-5.3.5- Report07
2.7 2.7.6-1 ( 3) Report16 R142E ( ) R142F R143J R143K R143L R143M ( ) ( ) ( ) ( ) ( ) R143N ( ) R143E ( ) R143A [ ( )] R1431 ( ) 51 250 mg 1 2 250 mg 1 3 500 mg 1 2 3 14 59 250 mg 1 2 3 250 mg 1 3 14 500 mg 1 2 8 250 mg 1 2 500 mg 1 2 15 250 mg 1 2 250 mg 1 3 500 mg 1 2 22 250 mg 1 2 500 mg 1 2 15 250 mg 1 2 250 mg 1 3 500 mg 1 2 24 250 mg 1 2 250 mg 1 3 500 mg 1 2 15 250 mg 1 2 250 mg 1 3 500 mg 1 2 11 500 mg 1 2 500 mg 1 3 18 500 mg 1 2 500 mg 1 3 1000 mg 1 2 14 25 19 8 7 9 7 14 7 14 14 ( 28 ) 14 12 8 4 7 13 14 19 5.3.5-19 Report08 19 19 20 20 20 20 20 20 20 20 20 20 20 20 5.3.5- Report09 5.3.5- Report10 5.3.5- Report11 5.3.5- Report12 5.3.5- Report13 5.3.5- Report14 5.3.5- Report15 20 20 20 5.3.5-20 5.3.5- Report17
2.7 2.7.6.1 2.7.6.1.1 1 () 5.3.3-Report01 2.7.6.1.1-1 2.7.6.1.1-1 1 25 mg () LD 50 2000 mg/kg 1/600 () 3 100 mg/kg 1/60 1 250 mg 1/10 2.7.6.1.1-1 DRPM ( 25500 mg60 ) 2550125250500 mg 2 ( 2449 5480 kg) DRPM DRPM 25500 mg 1 1 (60 ) (250 mg) (500 mg) ( ) ( ) (ASTALTAl-PLAPLDHγ-GTP A/G TTTZTTBUN NaKClCaPβ 2 -) (α 1 -β 2 -NAGNa KClpH ) ( ) () () * 19 () 19 () *
2.7 1 3 7 0 (hr) 1 1.5 2 3 4 6 8 12 24 DRPM (60 ) 12 ph a) b) c) d) (60 ) a) 500 mg b) 125 mg250 mg500 mg c) 2(810hr1012hr) d) 12 (1224hr) 2.7.6.1.1-1
2.7 1) 11 2.7.6.1.1-2 11 10 10 11 () 1 ()10 10 10 10 2.7.6.1.1-2 2) 10 ALT 1 7 DRPM 3) DRPM 25 mg50 mg125 mg250 mg500 mg ( 2 ) 60 Cmax AUC 2- t 1/2 (β) 1 70%(2.7.2.2.1.1.1 ) 4) 500 mg DRPM TLC- DRPM
2.7 5) 250 mg 1 1 ALT DRPM 7 DRPM 500 mg Cmax AUC DRPM 70% DRPM ( )
2.7 2.7.6.1.2 1 () 5.3.3-Report02 2.7.6.1.2-1 2.7.6.1.2-1 2.7.6.1.2-1 DRPM1252505001000 mg ( 1251000 mg30 ) 1252505001000 mg 6 ( 2645 58.581 kg) DRPM DRPM 125 1000 mg 1 1 (30 ) (250 mg) (500 mg) ( ) ( ) (ASTALTAl-PLAPLDHγ-GTP A/G TTTZTTBUN NaKClCaPβ 2 -) (α 1 -β 2 -NAGNa KClpH ) ( ) () () * 19 () 19 () *
2.7 1 3 7 0 (hr) 0.5 0.75 1 1.5 2 3 4 6 8 12 24 DRPM (30 ) 12 ph a) 24hr b) c) DRPM (30 ) a) 500 mg1000 mg b) 2 (810hr1012hr) c)12 (1224hr) 2.7.6.1.2-1
2.7 1) 25 2.7.6.1.2-2 25 24 24 25 () 1 ()24 24 24 24 2.7.6.1.2-2 2) 24 3 (γ-gtp AST ) DRPM 3) DRPM 1252505001000 mg 30 Cmax AUC t 1/2 (β) 24 DRPM 1000 mg 24 DRPM 75%DRPM (DRPM-DC) 90% (2.7.2.2.1.1.1 ) 4) DRPM 1000 mg DRPM TLC-
2.7 DRPM 5) DRPM DRPM-DC HPLC 24 () 125 mg 12.7%250 mg 12.1%500 mg 15.5%1000 mg 17.2% ( 2.7.2-2) DRPM-DC AUC AUC 250 mg 4%500 mg 6%1000 mg 7% 125 mg DRPM-DC DRPM-DC Cmax Cmax 250 mg 3% 500 mg 3% 1000 mg 4%DRPM DRPM-DC 24 90% ( 2.7.2-2 3) 6) ex vivo 2.5210.8% (2.7.2.2.1.2 ) 7) DRPM 1000 mg Cmax AUC 125 mg 1000 mg () 125 mg 1000 mg 24 75% DRPM DRPM-DC AUC AUC 250 mg 4%500 mg 6%1000 mg 7%DRPM-DC Cmax Cmax 250 mg 3% 500 mg 3% 1000 mg 4% (DRPM) DRPM-DC 90% 1251000 mg ( 30 2 ) 2.5210.8% DRPM 1251000 mg 125 mg 1000 mg
2.7 2.7.6.1.3 1 () 5.3.3-Report03 2.7.6.1.3-1 2.7.6.1.3-1 2.7.6.1.3-1 DRPM500 mg ( ) (1 500 mg 12 11 30 ) 8 ( 2 ) ( 2444 5571 kg) DRPM DRPM 500 mg 1 2 (30 ) 6 (11 ) ( ) ( ) (ASTALTAl-PLAPLDHγ-GTP A/G TTTZTTBUN NaKClCaPβ 2 -) (α 1 -β 2 -NAGNa KClpH )( ) () () () * 19 () 19 () *
1 3 7 25 6 0 0.5 1 1.5 2 3 4 6 8 10 12 0 0.5 0 0.5 2 0 0.5 0 0.5 1 1.5 2 3 4 6 8 10 12 24 36 DRPM (30 ) 12 ph () 34 34 34 DRPM (30 ) * 1 5 2.7.6.1.3-1
1) 9 2.7.6.1.3-2 9 8 8 9 () 1 ()8 8 8 8 2.7.6.1.3-2 2) DRPM 500 mg 1 2 6 ( 11 ) (30 ) DRPM 1 () DRPM 3) DRPM 2.7.6.1.3-2 2.7.6.1.3-3 DRPM EnterobacteriaceaeLactobacillus Streptococcus Enterococcus 7 C. difficile DRPM 1 4
2.7.6.1.3-2 () No. of aerobes (log CFU/g of feces) Isolate 1 3 1 7 Enterobacteriaceae GNF-GNR a) Streptococcus Enterococcus Staphylococcus Bacillus Yeasts Lactobacillus 7.1 ND b) 7.1 4.9 1.7 2.6 1.5 8.2 7.1 1.7 5.4 6.9 2.5 3.2 3.3 6.8 5.1 ND ND 8.5 3.3 3.5 3.5 3.8 7.3 ND 5.9 7.6 2.2 2.5 2.2 7.2 Total aerobes 8.8 8.0 8.6 8.6 a) b)not detected 2.7.6.1.3-3 () No. of anaerobes (log CFU/g of feces) Isolate 1 3 1 7 Bacteroides Fusobacterium Bifidobacterium Eubacterium Lactobacillus Clostridium Peptococcaceae Veillonellaceae 10.1 8.9 10.3 9.6 8.7 8.0 9.0 1.2 9.5 7.3 9.7 9.3 4.1 7.2 8.4 1.1 8.9 7.6 9.5 8.3 ND a) 5.9 7.3 1.1 9.5 8.0 9.8 8.4 6.8 6.5 7.5 2.0 Total anaerobes 10.7 10.2 9.9 10.4 a)not detected 4) DRPM 2.7.6.1.3-4 2.7.6.1.3-5 DRPM Streptococcus HaemophilusNeisseriaceae Bacteroides FusobacteriumActinomycesStreptococcusVeillonella 3 6
2.7.6.1.3-4 () Isolate Enterobacteriaceae GNF-GNR c) Haemophilus Streptococcus Staphylococcus Neisseriaceae Bacillus Corynebacterium Yeast Lactobacillus ND b) 0.4 5.2 6.3 1.0 5.2 ND 0.7 0.7 3.2 a) 1.5 0.4 ND 4.9 5.9 1.9 4.5 ND 2.7 1.2 2.6 No. of aerobes (log CFU/swab) 3 ND ND 4.3 5.0 3.4 4.4 ND 3.3 0.6 0.9 6 ND 0.6 4.0 4.4 2.1 3.9 ND 1.2 ND 1.3 1 ND 0.8 5.0 5.6 0.7 5.2 0.7 3.6 ND 2.0 7 ND ND 4.9 6.1 1.7 4.7 ND 4.5 ND 3.0 Total aerobes 6.4 6.2 5.3 5.3 6.1 6.3 a) b)not detected c) 2.7.6.1.3-5 () Bacteroides Fusobacterium Actinomyces Bifidobacterium Propionibacterium Eubacterium Peptostreptococcus Streptococcus Veillonella Isolate 5.3 3.8 4.2 0.5 ND b) 1.4 3.7 4.8 6.0 No. of anaerobes (log CFU/swab) a) 1.5 3 6 1 5.2 2.4 1.8 3.4 4.8 2.5 2.5 4.5 4.6 3.1 3.6 4.0 0.5 0.4 1.0 0.4 ND ND ND 1.0 1.8 ND ND ND 3.7 ND 0.8 2.2 5.2 0.4 3.1 3.6 5.4 1.9 1.9 5.2 7 4.3 3.4 3.8 1.9 ND ND 1.8 3.1 5.4 Total anaerobes 6.5 6.1 4.1 5.1 6.2 5.8 a) b)not detected 5) DRPM 500 mg 1 2 6 (6 1 11 ) 30 DRPM (2.7.2.2.1.1.2 ) 6) 500 mg 1 2 6 3.5512.7% (2.7.2.2.1.2 )
7) β- 3 1 DRPM DRPM (0.15 µg/g) ( 2.7.6.1.3.-6) β-2 1 1 ( 2.7.6.1.3-7) 2.7.6.1.3-6 DRPM Fecal concentraions (µg/g) Before Day 3 Day 7 ( 1 ) 1 <0.15 <0.15 <0.15 2 <0.15 <0.15 <0.15 3 <0.15 <0.15 <0.15 4 <0.15 <0.15 <0.15 5 a) <0.15 <0.15 <0.15 6 <0.15 <0.15 <0.15 7 a) <0.15 <0.15 <0.15 8 <0.15 <0.15 <0.15 a)placebo 2.7.6.1.3-7 DRPM β lactamase β lactamase activity Before Day 3 Day 7 ( 1 ) 1 5 3 2 2 1 1 0 3 5 4 5 4 0 0 0 5 a) 3 3 5 6 1 2 4 7 a) 4 5 5 8 2 2 4 ) β lactamase Nitrocefin (2E-n) a)placebo 8) Cmax 12 DRPM 2
2.7.6.1.4 1 () 5.3.3-Report04 2.7.6.1.4-1 2.7.6.1.4-1 2.7.6.1.4-1 DRPM1000 mg (1 1000 mg 12 11 30 ) 8 ( 2 ) ( 2541 5767.8 kg) DRPM DRPM 1000 mg 1 2 (30 ) 6 (11 ) (500 mg) () ( ) ( ) (ASTALTAl-PLAPLDHγ-GTP A/G TTTZTTBUN NaKClCaPβ 2 -) (α 1 -β 2 -NAGNa KClpH ) (CRP ) () * 19 () 19 () *
1 2 3 4 5 6 7 12 13 DRPM 1 2 3 4 5 6 7 8 9 10 11 CRP ph () () β 1 2.7.6.1.4-1
1) 10 2.7.6.1.4-2 10 1 1 8 10 () 2 ()8 8 8 8 2.7.6.1.4-2 2) DRPM 1 DRPM DRPM AST ALT 1 ALT 1 ALT LDH 1 3 DRPM DRPM DRPM
3) DRPM Enterobacteriaceae Enterococcus 7 BacteroidesBifidobacterium C. difficile DRPM 1 1000 mg 1 2 4) DRPM 1000 mg 1 2 6 (6 1 11 ) 30 DRPM (2.7.2.2.1.1.2 ) 5) 1000 mg 1 2 6 1.523.8% (2.7.2.2.1.2 ) 6) β- DRPM ( 34 ) ( 67 ) (0.15 µg/g) β- 7) DRPM (1 1000 mg 1 2 )
2.7.6.1.5 1 (500 mg 3 ) 5.3.3-Report05 2.7.6.1.5-1 2.7.6.1.5-1 2.7.6.1.5-1 DRPM 1 500 mg1 3 1 3 DRPM (1 500 mg 6 3 30 ) 6 ( 2125 53.270.0 kg) DRPM DRPM 500 mg 1 3 (30 ) 3 (500 mg) () () ( ) (ASTALTAl-PLAPLDHγ-GTP BUNNaKCl) ( )(CRP) () * 20 () 20 () *
2 1 1 () 1 7 () () 2.7.6.1.5-1 1) 10 2.7.6.1.5-2 10 1 1 8 8 8 1 1 6
10 2 8 2 ()6 6 6 6 2.7.6.1.5-2 2) DRPM 500 mg 1 3 (6 3 ) 30 () () DRPM (2.7.2.2.1.1.3 ) 3) 2 ( 4 ) DRPM 1 [ ()] 4) 1 3 DRPM
2.7 2.7.6.2 2.7.6.2.1 () 2.7.6.2.1-1 5.3.3-Report06 2.7.6.2.1-1 DRPM 2 ( 250 mg 500 mg3060 ) 20 14 14 13 () 13 () 12 1) 20 79 1) 2) 3) β- 4) 5) DRPM 6) 6 7) DRPM DRPM 1 250 mg () 500 mg () (3060 ) 250 mg 500 mg 1) 2) 3) 4) DRPM 1 2 Bioassay 1) 5) 3 5 123 45 12 3 ()
2.7 2.7.6.2.1-1 () () 6) 5 123 45 12 3 () * 4 19 () 19 () * 1) 14 13 ( 2.7.6.2.1-1) 1 () 14 14 13 1 1 ( 1) () 13 1 1 ( 1) () 12 2 2 ( 1 1) 2.7.6.2.1-1
2.7 2) 2.7.6.2.1-2 2.7.6.2.1-2 項目カテゴリー例数 性 13 年齢 60 70 5 70 80 8 () 69.9 () 4.9 () 61.0 () 72.0 () 75.0 体重 40 kg 50 kg 1 50 kg 60 kg 6 60 kg 70 kg 6 (kg) 59.2 (kg) 6.3 (kg) 46.0 (kg) 59.0 (kg) 69.5 性 13 入院 外来の区分 13 0 基礎疾患の有無 11 2 合併症の有無 13 0 治験薬投与直前の化学療法の有無 13 0 3) DRPM 250 mg 30 60 60160 0.7610.3 µg/g (8 ) 2.4210.2 µg/ml (8 ) 1 425.6% 15.072.4% (7 ) DRPM 500 mg 30 60 90130 1.044.51 µg/g (5 ) 5.5515.6 µg/ml (5 ) 18.749.9% (5 ) (2.7.2.2.5.4 ) 4) A) () () 13 1 () 250 mg 8 500
2.7 mg 5 13 B) () () 12 2 () 1 1 250 mg 7 500 mg 5 12 3 ( 25.0%)10 () 250 mg 1 ( 8.3%)4 () AST ALT γ-gtp β 2 5) DRPM 250 mg 500 mg3060 7-8)
2.7 2.7.6.2.2 () 2.7.6.2.2-1 5.3.3-Report07 2.7.6.2.2-1 DRPM ( 250 mg30 ) 13 (10 3 ) 13 13 13 () 13 () 13 20 70 1) 2) () 1) 2) β- 3) 4) 5) 6) 6 (DRPM ) 7) (HIV) 8) () DRPM DRPM 1 250 mg () (30 ) 250 mg 1) 2) 3) 4) 1) 13 1 2 2 4 3 4 2) () 15 30 1 2 4 6 Bioassay
2.7 2.7.6.2.2-1 () () 1) 5) 3 5 123 45 12 3 () 6) 5 123 45 12 3 () * 19 () 19 () * 1) 13 ( 2.7.6.2.2-1) 13 13 13 () 13 () 13 2.7.6.2.2-1
2.7 2) 2.7.6.2.2-2 2.7.6.2.2-2 13 30 40 1 40 50 5 50 60 3 60 70 4 () 52.0 () 10.5 () 37.0 () 50.0 () 69.0 40 kg 50 kg 3 50 kg 60 kg 6 60 kg 70 kg 4 (kg) 54.7 (kg) 7.6 (kg) 40.0 (kg) 56.0 (kg) 65.0 入院 外来の区分 13 0 13 0 7 6 13 0 13 0 3) DRPM 250 mg 30 50230 10 ( 8 ) 3 3 3 2 3 1 0.423.58 µg/g (7 ) 0.272.98 µg/g (7 ) 0.345.12 µg/g (7 ) 0.292.89 µg/g (8 ) 0.50 2.86 µg/g (7 ) 0.204.52 µg/g (7 ) () 0.1118.4 µg/ml (10 ) () 12.085.9% (7 ) 6.171.5% (7 ) 9.7122.8% (7 ) 10.361.9% (8 ) 14.261.9% (7 ) 12.8108.4% (7 )
2.7 () 1 µg/ml 0.1021.3 µg/ml (10 ) () 72.1 154.9% (10 ) (2.7.2.2.5.7 ) DRPM 250 mg 30 (3 ) 8.6352.47.90 µg/ml 1 (Cmax) 14.112.812.0 µg/ml ( ) 61.2409.465.8%(2.7.2.2.5.7 ) 4) A) () 13 B) () 13 5) DRPM 250 mg30 9-10)
2.7 2.7.6.2.3 () 2.7.6.2.3-1 5.3.3-Report08 2.7.6.2.3-1 DRPM ( 250 mg30 ) 10 12 11 10 () 10 () 10 () () 1) 20 79 2) 3) 1) AST 100 IU/L ALT 100 IU/L 2) 3) 4) β- 5) 6) 7) DRPM 8) 6 9) DRPM DRPM 1 250 mg () (30 ) 250 mg 1) 2) 3) 4) 1 2 Bioassay 1) 5) 3 5 123 45
2.7 2.7.6.2.3-1 () () 12 3 () 6) 5 123 45 12 3 () * 5 20 () 20 () * 1) 12 10 ( 2.7.6.2.3-1) 2 1 1 () 12 1 11 10 1 1 () () 10 1 1 () () 10 1 1 () 2.7.6.2.3-1
2.7 2) 2.7.6.2.3-2 2.7.6.2.3-2 項目 カテゴリー 例数 性 男 4 女 6 年齢 30 歳以上 40 歳未満 2 4050 0 5060 0 6070 4 7080 4 () 64.7 () 16.1 () 35.0 () 69.0 () 79.0 体重 40 kg 1 40 kg50 kg 1 50 kg60 kg 4 60 kg70 kg 4 (kg) 56.3 (kg) 9.7 (kg) 38.5 (kg) 57.5 (kg) 68.0 入院 外来の区分 入院 10 外来 0 基礎疾患 合併症の有無 無 7 有 3 7 無 10 有 0 3) DRPM 250 mg 30 45121 2.229.45 µg/ml (7 ) 58129 0.767.88 µg/g (9 ) 65143 0.253.42 µg/g (8 ) 67154 0.342.68 µg/g (4 ) 3.3315.6 µg/ml (9 ) 26.5% (1 ) 43.671.2% (5 ) 5.139.3% (5 ) 5.416.0% (3 ) 1 (2.7.2.2.5.2 )
2.7 4) () () 10 1 A) () 10 3 (30.0%)6 3 1 () B) () 10 6 ( 60.0%)13 AST ALT () 5) DRPM 250 mg30 11-12)
2.7 2.7.6.2.4 () 2.7.6.2.4-1 5.3.3-Report09 2.7.6.2.4-1 DRPM ( 250 mg30 ) 10 12 12 12 () 12 () 12 1) 20 79 2) 3) 1) AST 100 IU/L ALT 100 IU/L 2) 3) 4) β- 5) 6) 7) DRPM 8) 6 9) DRPM DRPM 1 250 mg () (30 ) 250 mg 1) 2) 3) 4) 1 2 Bioassay
2.7 2.7.6.2.4-1 () () 1) 5) 3 5 123 45 12 3 () 6) 5 123 45 12 3 () * 4 20 () 20 () * 1) 12 ( 2.7.6.2.4-1) 12 12 12 () 12 () 12 2.7.6.2.4-1
2.7 2) 2.7.6.2.4-2 2.7.6.2.4-2 7 5 2030 3 3040 3 4050 2 5060 2 6070 2 () 42.1 () 14.3 () 21.0 () 40.0 () 64.0 40kg 1 40kg50kg 1 50kg60kg 3 60kg70kg 4 70kg 2 1 (kg) 62.7 (kg) 15.7 (kg) 38.0 (kg) 61.7 (kg) 93.6 入院 外来の区分 12 6 6 7 11 1 3) DRPM 250 mg 30 6090 0.266.09 µg/g (5) 5.05 14.2 µg/ml (6 ) 2.742.9% (5 ) 60155 0.272.58 µg/g (6 ) 1.957.77 µg/ml (6 ) 6.133.2% (6 ) (2.7.2.2.5.9 ) 4) A) () 12 1 (8.3%)1 ()
2.7 () B) () 12 5) DRPM 250 mg30 13-14)
2.7 2.7.6.2.5 () 2.7.6.2.5-1 5.3.3-Report10 2.7.6.2.5-1 DRPM ( 250 mg30 ) 10 10 10 10 () 10 () 10 1) 20 79 2) 1) AST 100 IU/L ALT 100 IU/L 2) 3) 4) β- 5) 6) 7) DRPM 8) 6 9) DRPM DRPM 1 250 mg () (30 ) 250 mg 1) 2) 3) 4) 1 2 Bioassay HPLC
2.7 2.7.6.2.5-1 () () 1) 5) 3 5 123 45 12 3 () 6) 5 123 45 12 3 () * 20 () 20 () * 1) 10 ( 2.7.6.2.5-1) 10 10 10 () 10 () 10 2.7.6.2.5-1
2.7 2) 2.7.6.2.5-2 2.7.6.2.5-2 8 2 20 30 4 30 40 3 40 50 2 50 60 0 60 70 0 70 80 1 () 35.9 () 14.2 () 22.0 () 31.5 () 70.0 60kg 70kg 2 70kg 80kg 1 7 (kg) 65.7 (kg) 8.1 (kg) 60.0 (kg) 62.0 (kg) 75.0 入院 外来の区分 0 10 0 8 2 7 9 1 3) DRPM 250 mg 30 3070 2.293.15 µg/g (7 ) 6.48 18.1 µg/ml (10 ) 15.736.9% (7 ) (2.7.2.2.5.1 ) 4) A) () 10 B) () 10 2 ( 20.0%)2
2.7 () BUN () 5) DRPM 250 mg30 15-16)
2.7 2.7.6.2.6 () 2.7.6.2.6-1 5.3.3-Report11 2.7.6.2.6-1 DRPM () ( 250 mg30 ) 5 5 5 5 () 5 () 5 1) 20 79 2) 1) AST 100 IU/L ALT 100 IU/L 2) 3) 4) β- 5) 6) 7) DRPM 8) 6 9) DRPM DRPM 1 250 mg () (30 ) 250 mg 1) 2) 3) 4) 12 Bioassay 1) 5) 3 5 123 45
2.7 2.7.6.2.6-1 () () * 12 3 () 6) 5 123 45 12 3 () 20 () 20 () * 1) 5 ( 2.7.6.2.6-1) 5 5 5 () 5 () 5 2.7.6.2.6-1
2.7 2) 2.7.6.2.6-2 2.7.6.2.6-2 2 3 40 50 0 50 60 1 60 70 1 70 80 3 () 67.4 () 9.8 () 52.0 () 70.0 () 78.0 40kg 50kg 1 50kg 60kg 3 60kg 70kg 1 (kg) 56.3 (kg) 5.1 (kg) 49.5 (kg) 56.0 (kg) 63.0 入院 外来の区分 4 1 0 5 7 0 5 3) DRPM 250 mg 30 70115 0.160.87 µg/ml (5 ) 6.86 12.9 µg/ml (5 ) 2.310.5% (4 ) (2.7.2.2.5.8 ) 4) A) () 5 1 (20.0%)1 () B) () 5 2 ( 40.0%)2
2.7 () 5) DRPM 250 mg30 17-18)
2.7 2.7.6.2.7 () 2.7.6.2.7-1 5.3.3-Report12 2.7.6.2.7-1 DRPM ( 250 mg30 ) 10 10 10 10 () 10 () 10 () 1) 20 79 2) 1) AST 100 IU/L ALT 100 IU/L 2) 3) 4) β- 5) 6) 7) DRPM 8) 6 9) DRPM DRPM 1 250 mg () (30 ) 250 mg 1) 2) 3) 4) 1 2 Bioassay
2.7 2.7.6.2.7-1 () () 1) 5) 3 5 123 45 12 3 () 6) 5 123 45 12 3 () * 20 () 20 () * 1) 10 ( 2.7.6.2.7-1) 10 10 10 () 10 () 10 2.7.6.2.7-1
2.7 2) 2.7.6.2.7-2 2.7.6.2.7-2 4 6 2030 6 3040 3 4050 0 5060 1 () 29.7 () 9.6 () 20.0 () 26.5 () 54.0 40kg50kg 4 50kg60kg 3 60kg70kg 3 (kg) 53.3 (kg) 9.6 (kg) 40.0 (kg) 51.5 (kg) 68.0 入院 外来の区分 10 9 1 7 9 1 3) DRPM 250 mg 30 70105 0.342.19 µg/g (7 ) 2.555.60 µg/ml (6 ) 14.347.9% (6 ) 6075 0.361.10 µg/g (3 ) 4.085.15 µg/ml (3 ) 7.721.4% (3 ) (2.7.2.2.5.10 ) 4) A) () 10 B) () 10 4 ( 40.0%)4
2.7 () 3 ( 30.0%)3 2 1 5) DRPM 250 mg30 19-20)
2.7 2.7.6.2.8 () 2.7.6.2.8-1 5.3.3-Report13 2.7.6.2.8-1 DRPM ( 250 mg30 ) 5 6 5 5 () 5 () 3 1) 20 79 2) 3) 1) AST 100 IU/L ALT 100 IU/L 2) 3) 4) β- 5) 6) 7) DRPM 8) 6 9) DRPM DRPM 1 250 mg () (30 ) 250 mg 1) 2) 3) 4) 30 ( )2.54.56.5 HPLC 1) 5) 3 5 123 45 12 3 ()
2.7 2.7.6.2.8-1 () () 6) 5 123 45 12 3 () * 2 20 () 20 () * 1) 6 1 ( 2.7.6.2.8-1) 6 1 5 5 () 5 () 3 2 2 ( 1 1) 2.7.6.2.8-1
2.7 2) 2.7.6.2.8-2 2.7.6.2.8-2 4 1 30 40 1 40 50 0 50 60 1 60 70 2 70 80 1 () 59.4 () 15.1 () 38.0 () 63.0 () 79.0 40kg 1 40kg 50kg 1 50kg 60kg 2 60kg 70kg 0 70kg 80kg 1 (kg) 53.8 (kg) 13.5 (kg) 37.0 (kg) 53.0 (kg) 73.0 入院 外来の区分 5 2 3 7 5 0 3) DRPM 250 mg 30 2.365.17 µg/ml (5 ) ( Cmax) 10.524.4 µg/ml (5 ) ( ) 14.447.3% (5 ) (2.7.2.2.5.6 ) 4) A) () 5 B) () () 3 2 1 3 2 (4 )
2.7 AST ALT 1 () 5) DRPM 250 mg30 21-22)
2.7 2.7.6.3 2.7.6.3.1 5.3.3-Report14 2.7.6.3.1-1 2.7.6.3.1-1 2.7.6.3.1-1 DRPM 1 250 mg ( 250 mg30 ) 6 65 ( 6669 57.069.9 kg) DRPM DRPM 250 mg 1 1 (30 ) 250 mg () ( ) (ASTALTAl-PLAPLDHγ-GTP BUNNaKCl ( ) (CRP) () * 20 () 20 () *
2.7 () (hr) 0 0.5 1 2 4 6 8 10 12 24 a) a) b) c) b) 0.5 a)b)c) 2.7.6.3.1-1 1) 7 2.7.6.3.1-2 7 1 6
2.7 7 () 1 ()6 6 6 6 2.7.6.3.1-2 2) ( 250 mg) (2.7.2.2.2 ) 3) 1 4 () 1 () 12 4) DRPM 8 4 ( ) 1 () 12 ()
2.7 2.7.6.3.2 2.7.6.3.2-1 5.3.3-Report15 2.7.6.3.2-1 DRPM 12 12 12 12 () 12 () 12 1) 20 79 2) 3) 4) 70 ml/min 1) 2) 3) 4) 5) β- 6) 7) 8) DRPM 9) 6 10) DRPM DRPM 1 250 mg () (30 ) 250 mg 1) 2) 3) 4) 1) 30 ()1 2 4 6 8 12 24 2) ()2 24 46 68 8 12 1224 Bioassay HPLC 1) 5) 3 5
2.7 2.7.6.3.2-1 () () * 123 45 12 3 () 6) 5 123 45 12 3 () 1) AUCCmaxt 1/2 2) 20 () 20 () * 1) 12 ( 2.7.6.3.2-1) 12 12 12 () 12 () 12 2.7.6.3.2-1
2.7 2) DRPM ( 250 mg) (CLcr) AUC 1.53.3 (2.7.2.2.3 ) 3) 8.3% (1/12 ) 1 4) DRPM 250 mg DRPM DRPM 250 mg