1G) Yos~12t C1984) Rifampicin2] £487] AX0| BASt BEE = © &-& &£ at DEAR: AS Be - DEAS RE Studies on Bioavailability of Rifampicin Cheol Kyu Lee and Jae Back Kim’. ‘The bioavailability of rifampicin (brand A,B and C) was studied and the dissolution by foemed plestic rotating method end basket rotating method was. also investigated, The results were as follows; 1. In the case of foamed plastic rotating method, it was revealed that disso- lution rate of brand C was most rapid, but in the case of basket rotating method the results reveled that brand B was most rapid, Also it was observed that the dissolution rate in artificial gastric juice was more rapid than one in artificial intestinal juice, and that Avicel added in capsule Increased additively the dissolution rate, particulary brand B. 2, Relative systemic availability by urine data showed that the results from all capsules filled with brand A,B and C were identical but in the case of the ripamficin capsules filled with Avicel, the results showed that Avi- cel increased the availability of brand A and B, 3. Area under serum concentration curve (0~8hrs) was in order of brand A ‘brand C > brand B, but Avicel increased significantly the AUC of brand B and showed no effect in others. 4, Relative systemic availability calculated with excreted amount of rifamp- icin in urine was similar in each rifampicin capsules, In rifampicin (A) and rifampicin (B), Avicel which added in capsules appeared increasing tendency in urine excretion of rifampicin, but in rifampicin (C) it did not appeared, Area under serum concentration curve (O~8hrs.) in rifampicin capsules was in order of rifampicin(A)*srifampicin(C)> rifampicin(B). In rifampicin (B) with Avicel capsules, area under serum concentration curve (0—8hrs. ) increased significantly and in others insignificantly. ~ Graduate School, Won Kwang University *College of Pharmacy, Won Kwang University — 10:106 Rifampicin§) Le AUia] Ra BSE Vol.14, No.8 Rifampicin@ Streptomyces mediterraneiz #r] Ge rifamycin BS] PAR FS W524] Grambitt, GrambSt bacteria 3] mycobacteriacl fp /S3Hs Ste IALE. iPeHAHe ol de) FSs1a stat ol Fe SAAS) sbi: HELA RE Sol RA REALS oak #50] 3—formyl rifamycin SV7} six} pH 7.069.001 #2 Ne(cs|¢1 rifampicin quinone] Sic}. Rifampicin(¢]3} RMP) 2 Eo} REI] a] WAEEE pHe|EAe] Sop pH 2. 1204 41 10-7g/100mL0)2. pH7} 9.032.2 Sb ahol wo} WEMIEE oF ho-R athe, pH 9.3~ 7.389 4% 0. 11~9. 15g /100mI 3 =z MBH: ©] e}. REM MS MOWAT AS AAS ABTS) wu = BepS] EHIME 9} Sat Sm, Et ARS] AAAS] BA BA vale Able] deals 2A Sahel MM iy] WML S Sal Azz] A leita Wete] A1Zs|z gle. all AN RARE Sa AlrS Ue? Awe BAF (eel Babe wale? aaa Wik complex® Miehic Wal PP] Heese. 222 @S RMP) arginine complexd Miliso}] MES SralRow] ee AH M2 PVPS}S) steko] RMPS| WIRES Qala] SrpAllepOe HRMS LL vb ake. ‘GAL RMP2} formulations Yee «| WAHAB e]ale Aol] oe EZ} Ma- nnisto QE AtzBesrol ose] ML wh leh. 6] RNAS (6H! S BH RMPe} YAS AWA] M—epe Y He go. EZ 7y9] RMP AE sto] Hy MLR A, MUR} AIRS Baste] oles) ALGAE RHAD FAT] LMADHS Hee loxl cbse] val Ada gsorg Bont leh VAS Vas Mas] AS MRS Rss vpolep. RRA EK MAD ME —Rifampicinek TS Hw MmMRMy yet rifampicin brand A(o]s} RMP (A)), rifampicin brand B(o]8} RMP (B)) rifampicin brand C(o]3} RMP (C))9} ABA & U.S. standard screen sieve 2 YJ 74~149¢mq] BPS Vo] RHE AR alt. 25] MMe RMP BBS QF, 4 RMP s00mg4s 6% HM 30OmIe YEREAL AA RMP HHO. aoleh. RMP 34 MMS 9%, 2 RMP i50mee FaROe 1 aol At Saletsle. Avice wing RMP 79} MBL 2 RMP 150mge] Avicel 15mg, Avicel Somg st Avicsl 6024 & 47 34-37] WS rebo] sHiMS] Avicelg gnet RMP a-ak RMPHQSeptember, 1984 + a e a A 107 9 MS Lees BMA. QEaQ G44 Fez (foamed plastic)’ 224) 7} lomm, w7J 1%.5mm, We] 32 mm, if 13.5x5mm] ~#at 2713+ BR LIFES AMER URRY Beays A Batt. a1 (pH oF 1.2, KP), a2 (pH o 68, KP), ald ¢o(pH 7.0, KP W) SS HAMS] MMA SE 0.005w/v% polysorbate 80-2 FMe AI 1 w/v% polysorbate 80% Hine A) 2 YS GMM S Bx, 42} 50Om/S HHSZIe] VS TES SHINAI lal RMPS} Ft BLS] ascorbic acid-¢ YFHIMRRLel gM} ott. Ascorbic acid (G.R. Ciea, Kanto Chemical Cc. Inc), micro crystalline cellulose (Avieel® pH 101, Asahi Chemical Industry Ci Hayashi Pure Chemical Industry Co. Ltd.)@ (#Fit}g1°>] BREE Beckman DU-g uv- 0.005 Ltd), isoamyl alcohol (E.P., Hanawa, visible spectrophotometer (U.S.A.) with variable speed peristaltic pump (Har- vard Apparatus), dissolution test station & dissolution test unit (Hanson-Research Corp., U.S.A.) and dissolution drive control & regulated bath circulator (Hanson- Research Corp., U.S.A), spectrophotometer (MPS-5000), X-ray diffractometer (Rig- aku Corp., Japan), infra-red spectrophotometer (Jasco A202, Spectroscopic Co., LTD), pH meter (Analysts Omnimeter, Model OM-IA, Toa Electronics LTD. Japan) standard screen sieve (Yamato scientific Co., LTD. Japan.), phoenix-syringe with needle (disposable sterile non pyrogenic), dissolution tester (Erweka-apparatebau, G.m.b.H West Germany), Multifit interchangeable syringe (Waters Associates Co. ). Xe 81 AWezI— RMP 2YS mounto) ey Fat Ni filter, 95KV, 20mAz Xl ala ages estat. IR AMSeH— RMP ¥5} 1mgs} AxA]z] KBr Gish 100mgS fs] B}APApPoljAl Bay ep] E4174 600kg/cm*s} MELE pelletS FYeta) Zale c}S 7 HS] IR AME ay & wets. HMMA} 2] Rifampicing| ~eH—RMP 100mg 2Ys}o] 0.005w/v% polysorbate 80S BM A124, 0.005w/v% polysorbate 80S Hie A2YS 7s] mie} 10~80 meg, 30~240mege] JES ]4etT A75nmoll]s] RKKS Meso] RMS HRY Fh. in vitroWel4|2] BE say Fo] RMP WEEE Wo} Be yo =e BERS Metabo} ERA. Rifampicine| SH Be— EAL SARS LSA SabaS] MRS We HS 7lo] HUE 500m Asx HES] ES 3740.5°CR Hlstghet. wbys) sad AS Ads} SUS MSs} Ae we2mm7} eH hx aaAsFe FAH] G7} 9} FAVE] Fol] 2mm 6] Gelz|z] Se Mal} ARS Wye F WS Maks) et %zs}o] Cu target with108 Rifampicin’} MAUR MARE BE, Vol.14, No.3 | WHER 717 RMPS} fl—@ M5] ascorbic acid WIMFol 7-819 =}, RMP 50mg EAUSEY WEY Se AUel loading4j7 Aal Fol YS HK 120, 20rpmez aad AAA —seneMbT RS] Ast Jags Absbe] Szelz, 71414] 10mm dela all Wass] HWS Alals-e] millipore filter (3gm)Z WHA WSS) RMP BES MEM! >] 2 SUM aste] WMTAAE MES 33) Wbsbeley. HAL AMS AE AAAS] WMRMRS BAS Yale Yr 50, 150rpmos VSY WEA FIAT S EU Ea RRS Le WIRES BTS. RRNR— LOAN A1Yol AVS a SMT AWK AAA Saye Table 1s} dep a S RMP H°—RMP loomes BH3}7] Aso] SHFS mid 1,2,4,6,8mege} ASH AAA SSAS MHA 4S MUA Imlo] SH+ BE A MKS ZY Im/s WEAS UY USA(PH 7.0) Im’ 7}3}4} 3m/9} isoamyl aleoholz PES}ebZ a4) EAQE F1SISE Ape] 475nmol 7] RES Meo] BRRS frets. 74 Ae BRS 1~8meg/ml 9] col ERS] ows MH RMP REAL | wa S Aes. RS RMP €H°—RMP 100mes BPA] a VSA(PH 7.0)22 mi} 10,20, 40,60, 80mege] HEH SA sho] LEYS MMe. RR emlol Maka ASA 7.0) HE A WS LEY im’e Ye p< Als] isoam- yi alcohol? AGES ULLAT F HASSE Ashel 475nmo] 7 MIKES Bees} | RARE fe. 7A Ce HRS 10~80mcg/m! YY] ghey EsHES] Waoes Rs RMPst 9 OS Ssh. RS Pa ME RANGA] MAA AMS} AH bale eRe Rg PHS Fi YESH 2 WAT eel MEAG RMP 300mgol ages MARCY IES] Bt = 900mis} YAS HSA RS MH HR MM CALT)S} HHT 2,4,6, 9M) HAL the] RLS 7) Sea RMP WES We}. RHE TWH Ase Tally yyoR ‘Table I—The List of Human Volunteers Subjects Age(yrs) Sex Body Weight(kg) Height (cm) Smoking Drinking YO 2h M 65, 172 - - cH a M Co 168 - + cK 30 M 66 176 - + YS 26 M 63 172 + + cy 26 M 69 178 + + SH 3 M 63 170 = +September, 1984 sot go og A 109 AH. oh ML RMPS| dress ALEKS HELL Weal HTsbel dese Nie} Let 1, 2,4,8RFIMo] phoenix syringe o]-Bs}e] YYy smi42 Asx 30¥%t Yale +S 3000 TPM 1A VILA) HUES FAL FH MHS] BMS Heep. MART RO — A HS] SREY Seb] hep PLE M FS rule ose} Alabspolet. 8S EMAAH OS RATAN] GS MMPS He] 7/2] 3H ol2} He Be] ebealsht o] Bwhol i 2} seh) ea) Babe] Bast} AS RS PALMA} ite MMT iS Ze] relative systemic availabilitys} relative bioavailability Rs}si+t. trapezoidal BR BR Rifampicing| X49 IR ABS RMP Eel ase] MEE XA aa agg + (LT# 57. 25°01] RMP(B), RMP(C) 2% peak>} Yepster} RMP(A) oA HE}Y Al Skee} (TA 35. 5°24] RMP(A), RMP(B), RMP(C)2] ¢2.2 intensity7} S7}3} AD, WH 30°o]4] RMP(A), RMP(C), RMP(B)¢2. = intensity7} S7}3}l2r] ab Aq] SWE patterne Bsteh. EG 4 RMP ol ulspo] KBr pelletikee MT IR AMES AWshov} b+ 1700 —1760cm"', 1640—1660em~‘ol] RMP(A)3z RMP(B), RMP(C)$} intensity7} HAPS. ay lee Avbaiel IR Aw=Eale wgkrh. BSS Yes Hens O1Sst Rifampicin Seo] BWRR—A1 Aol Pe MM 224 RMP 22 somged 153 VEY Ze}Aol loading+]7| 0.005w/v% polysorbate 80S HRM 11 Yoh cH sbo} HE BUA C(L20rpm)-S @ MRE Fig. 13} abe. RE Val lke | RMP(C) 68.63%, RMP(B)+ 61.42% 7} HIN Siglo RMP(A) E A7.22%2 LSE YLT Yepsicr| 2 9]9) pyle RMP(C), RMP(B), RMP (A)o] E22 wise] Aa salep. 4 4 RMP SYS BF BOLO 80% old wHislotet. Al 2 Yo} He HBS 24] RMP Wet 5omg-S IGY weX4 Se-Ado] loading4|7 AM AHO} csho} MSA (20Orpm)-z a MIRE Pig. 2 0.005w/v% polysorbate 80: 3} eh. a) 2 Yo 4s RMP(A), RMP(B), RMP(C) SF 712] HARE GAS Ye} ash 2 ul, GOL A 50% U7} WEA, 120%} 60% UA7} WHO] VS HS Heby a4. QR, MEQ VEY SHAG S oa a1 Ys apa Holl] o) RMA] RMP2} shal0 Rifampicin®| 4 AAUBRe| PAR BIE Vol. 14, No.3 vy one a a ee wan ® Figure 1—Dissolution rate of rifampicin in Figure 2—Dissolution rate of rifampicin in artificial gastric juice with 0.005 artificial intestinal juice with w/¥% polysorbate 80. 0.005w/v% polysorbate 80. SIM AMBwoy lst gallo] HR B—A] 1] sl a]2 hol ale wt S4] RMP RAL chee} 0.005w/v% polysorbate 80-& HAM a] 1 fol whet UHHBCHACSOrpM)s} 0. 005w/v% polysorbate 80-& Bima 2] 2 ol Ae WHAWR(SOrpm) = a ER Fig. 35+ at. ALL Qo 7\S) RURRURE Mel 15tbel|4] RMP(B)E 94.35%7+ wie ulste] RMP(A) 22] RMP(C)= 60% vi9]z RMP(B)7} 7} te] HSI 2m] 2} Heel] 30% Fell = EF 00% late] WHS Art. UA M2 YAS] RRMRS Bel 15204] RMP(B)7} 18.72% yids »lete] RMP (A), RMP(C)%= 47} 9% AE] WHARS Hebe] RMP(B)7t ee] WSO AR SF BAMA 50% WSI7E MSAD 60 Fol 90% olbe] wisi. RMP(A) 3h89] 114% WHol =]alse Avicels} Q@ee2] RMP(A) 3B Avicel + na RMPCA) tol she} 0.05w/v% polysorbate 80-E Bima 1 kel HL WE RA (SOrpm)- % HARE Fig. 49} eh. HERE Bel 10% Fol AvicelS dne--] eb-2 RMP(A) AAlollAle VeHHlae] 29.56% ¥] visto} Avicel 15mg& ME YH 58.40%, Avicel 30mg-z Vesa AF 62.99%, Avicel omg Witt 734 80.48% = Avicels] in7} WHEE AEESMA Stas ¥, Avicels| He] S7Htel spe} co] SMES] Sohe Mebast. o] ARS RAST EMA AAleherl wt olfols BF 90% clase] wisi. RMP(B) HA 4 14H Yio) »] Ale Avicels] 9eo=%] RMP(B) BA 3 Avicel-e ‘WIM RMP(B) Adel AHs}o] 0.005w/v% polysorbate 80-S wna A 1 Noy MAL weySense ul ar) Figure 3—Dissolution rate of rifampicin ca- peules in artificial gastric juice with 0.005w/¥% polysorbate 80 and artificial intestinal juice with 0.005% /¥%_polysorbate 80. o—o, RMP(A); +) RMP(B); ++, RMP(C) in artificial gastric juice with 0.005w/v% polysorbate 80. ©, RMPCA)S +, RMP®); +, RMP(C) in artificial intestinal juice with 0.005w/v % polysorbate 80. Key: @(50rpm)-& at fs Fig. 59} Qe}. fos Bed SE Fol Avicel yehrs}4] ge RMP(B) gdels HelsHe] 7.74% aL visto] Avicel 15mg wat 27 8.40%, Avicel 30mg-Z WME 2+ 49.11%, aes es Figure 4—Dissolution rate of rifampicin ca- psules in artificial gastric juice with 0.005w/v% polysorbate 80. e——e, RMP(A) +——-+, RMP(A)+Avicel Ismg *——*, RMP(A)+Avicel 30mg «——s, RMP(A)+Avicel 60mg Key: Avicel Come Hig 734- 53.10% = Avicel 30mg o]4} Ko} GUMS ARES Salat 24), Avicels| sie] S7}etol te tien) Figure 5—Dissolution rate of rifampicin ca- psules in artificial gastric juice with 0,005w/v% polysorbate 80. Key: >>, RMP(B); +, RMP(B)+Avicel 15mg; +4, RMP(B) +Avice 130mg; oe, RMP(B)+Avice l6omg. % wie) Sree est. Poy” Figure 6—Dissolution rate of rifampicin ca- psules in artificial gastric juice with 0.005w/v% polysorbate 80. oo, RMP(C); + RMP(C)+Avicel 15mg; *—*, RMP(C)-+Avicel 30mg; o——s, RMP(C)+Avicel 60mg. Key:12 Rifampicin 9} 4:xFUaiol BEE BE Vol. 14, No.3 o] ARS MRE lA Alsigowl, 15k Fol VF 90% else] WISI Ad. RMP(C) BAS] ALAS Wille Plas Avicels] Ye}o z*| RMP(C) Aa wl Avicel-s aM RMP(C) z}Alel este} 0.005w/v% polysorbate 80% HAM V1 Yol A WHR GOrpm)-S % ASH Fig.63} Arh. RS BA Se Fol AvicelS Weta] Ge RMP(C) BlolA= wHiHel 7.25% a Ul ¥]e}o] Avicel 15mg Hoe 3 25.81%, Avicel 30mg-% inet 24 27.05%, Av- icel Omg Bima 34 50.46%R Avicels} Kinz} WME wieslAl Stlaow, Avicels} ko] $7} bell sbek oH) S7hE ebisct. oO] abe SRIF 10. EAA) AAAMoMl, [We Pole ZF 90% elte] wilislaAct. old AL Moly Avicele wangt RMP Zale et WMRGRE ses 7b il A\ Avice 9) in7} SHES Bale] S7t4]2| Avicels) Hel S7Htel eb co] Sy WUE) SME He}igte}. ze] 20% ASIA] BF 90% ol-se] seHLsle} Alaleael SadolA] t As Abe + Uatet. RMP(A) 3422) a2 YS Bitiel elle Avicels] G@oze RMP(A) Fad 2 Avicel “© HM RMP(A) Aol H}s}4] 0.005w/v% polysorbate 8k Wie a2 Hol Hak He IMARWR(1SOrpm)S et LE Fig. 75} Ze}. che) MIRE Nal 15% Fell Avice sone] ge RMPCA) Ale aie WHaRe] 9.56 Bw wlshe] Avicel 1smgs we AF 18.38%, Avicel somes Rina 34 18.99%, Avicel 6omg% imal 2% 99.23%. ZF AvicelS] HM} WHEE ARIESLAl Sh} Aoi Avicels| ste] S7bibel wee vl EWES] Sze Uebueb. ] ASRS Bt Fe 4077] Arlee] COL Hels BF 90% olate] HHS. a. a Figure 7—Dissolution rate of rifampicin ca- Figure 8—Dissolution rate of rifampicin ca- poules in artificial intestinal ju- psules in artificial intestinal ju- ice with 0.005w/v% polysorbate ioe with 0,005w/v% polysorbate: 80. 80. Key: mn, RMP: Key: =—n, RMP(B); + RMP(A)+Avicel 15mg; ——+, RMP(B)+Avice mg? *—+, RMP(A)+Avice 130mg; +—*, RMP(B)+Avice 130mg? a——a, RMP(A)+Avice 160mg. 2—, RMP(B)+Avice 160mg.September, 1984 + Al 3 RMP(B) 34l9] 24S yo vale Avicels) Qa} z4] RMP(B) Zl ¥ Avicel wma RMPCB) Alo] este] 0.005w/v% polysorbate 80 wing a] 2 el] HR WH WC5orpm)-S e HR Fig. 85} ach. Fol Avicel-= wins) ie RMP(B) shale Alt wie] 18.72% ale] visto] Avicel 1mg-$ wma AF 23.23%, Avicel somes Apa 44 42.53%» Avicel 60mg-& #in@ 73-7 89.24% = Avicels} wSin7} WRK. te shal | Avicels} tke] S7bitel we} vr] yee!) Sp ol BARS PRUNE 407A] AARshom| COR Pole RMP(C) 4 uebaisteh. LF 90% ole} sfitistaiet. 19) ALAS ilo) vals Avicels} Qe224 RMP(C) FAY Avicel & Hime RMP(C) gol alee} 0.005w/v% polysorbate 80% Hse Al2 Hel oe HRC5Orpm)-2 eb RRS Fig. 99} beh a *d 202 Fol] Avicel& ebnst-] ge RMP(C) ahalol lis YeHLELe) 28. 45 % Axl | 8-e] Avicel 1smg< wet 734 37.72%, Avicel 30mg- aE dF 53.91% Avicel 60mg HRMNet 724 84.39% 2 2 Avicels) Bein} weHFEL EMESLAL S7tA Asx] Avicels| Hel S7bol wpe} r] Z yGINAMES] SHE elas. ol 7S FFE OLA] Balser} GO Holt SF 90% lao} WIR. Figure 9—Dissolution rate of rifampicin ca- Figure 10—Dissolution rate of rifampicin with poules in artificial intestinal jui- Avicel 60mg capsules in artificial ce with 0,005w/v% polysorbate gastric juice with 0.005w/v% po- 80. lysorbate 80 and artificial intest re——o, RMP(C); inal juice with 0,005Ww/v% poly- ~ +, RMP(C)-+Avicel I5mgi sorbate 80. +—+, RMP(C)-+Avicel 30mg; Key: 20, RMPCA); 2s, RMP(C)+Avicel 60mg. : RMP); RMP(C) in artificial juice with 0.005w/v% *, RMP(C) in artificial intestinal juice with 0. 005w/v% polysorbate 80.ua Rifampicin | A:tOAURaS Bae BES Vol. 14, No.3 o]a a2 Hola] Avicel' HiMgt RMP plo] YR WHEW BILE eee ebed zh the Ay Avicel 2] ¥EDI7} WME AAs] S7t-]Ao] Avicels] fe] S7}tel we} vy Zw WES] Sb UEP. 2S. 6OF UelA] BF 90% e] ate] ane ol RE ALANA] RSH Hew ALL YS: BF 20% Vista 90% olate] HEH ARS ALAAAT OOF Hel 90% ole] WHisike=es Avicels| wht iene SAAS AHL A244 vo] S aaa AIS Ax Ya BH. Avicel 6omg#iin RMP Zl] a] 1% 2 a2 ell VR WHS MRS LeNsh7) Seb o] AR MIRE Fig. 109} Ae}. Avicel 60mg ¥in7} WHA Hl Als BBS A eel fA al 1 el] Oe ol RMP(B) 4] Hille] 90.01% ele] »]8he} RMP(C) 83.99%, RMP(A) 80.48%. RMP B)7 AS HE WME Vl Fao] o] QRS AvicelS Bist] Se MAT WAG RY BART. UA 2 HoPAAS 15% Fol] RMP(B)] WHsHo} 89.24% 41 c] v]sbo] RMP(C)+ 69.87 %» RMP(A)%= 39.23% RMP(B)7} 7} We] HEH s|s) oe] Ss] RMP(B)7} Avicelmin of lait a2 Fol 4s] we 7} Aaa] Srtsisiep. RS PRR WE —Rifampicin wks} rifampicin as] RHOEA~) RMP BW RMP 242 BAL + RF Hike RMP RES West] RS] PA RMP SHS RAR AL BFR RH He Fig. 11,129 Bh. MRE BW RMPS| RS PHMLMS Se Sets] +E Re] RMP wes HAMS | + RMP(A)ol4] 18.11%, RMP(B)= 16.52%, RMP(C)E 16.85% -fbs}glz. RMP ALE WRB AF RMP(A) 11.65%, RMP(B)E 11.76%, RMP(CHE 10.63% 4 MH tho] AS) wRetslep. RMP2| SAGAS WELZ] Sse] Hees YAKS Waetslo} RMP wets} RMP 3b ANA 2 7 AE BeNE HR BRE Lat + glgloo| 4 ase] relative ‘uf lia | i viral Figure 11—Human urinary excretion of total Figure 12—Human urinary excretion of total rifampicin after oral administ- rifampicin after oral administr- ration of rifampicin solution. ation of rifampicin 300mg capsules. Key: 02], RMP(A); mum, RMP(B); Key : (] RMP(A) ; mut, RMP(B) 222, RMP(C) eee, RMP(C)September, 1984 eran bees deer Sez ns Figure 13—Human urinary excretion of total rifampicin after oral administration of rifampicin 300mg with avicel 120mg capsules. Key :), RMP(A); sw, RMP(B); see, RMP(C) systemic availability(RA)S #S1at is RMP(A)= RA=0.643, RMP(B)= RA= 0.712, RMP(C)% RA=0.6319]3i+4, Rifampicin 3}]3} Avicel & Me rifampicin YA HH. & Rim RMP Aas RH F RS PARAS RMPA| RES RMPSe Besta He ADRS PAE eR Fig. 135} ct. Avicelo| int EMAAR] ol SS AR HRS SRE Seb] Ss PH 24 A BF AMM BRS WAL + Aaorl ea olds] HRS RMP eH, RMP 3}41 2] Avicel iinajl RMP Bal HH FF RS PHILS 7} RMI ste} ieee ‘ated Fig. 149} 2c}. 1S) RS BRIER 22] RMP @4] 8 Avicel Eso] MRS ol Pel Ae petrated Say Shs | PRO 2 FL RAG zi2} RMP(A)=0.643, RMP(B)=0.712, RMP(C)=0.631 9192.54 Avicel®) Hiins RH ORE Wad + dele RAS Sle AGE vol Feet. th¥S Rifampicin KE WE —rifampicin pis} rifampicin Was) Wwe 241 RMP ae RMP 242 BME F sth S RMPol i WHE MURS Fig. 15,165} 2}. RMP 2] ATFel F Hehe] aefl RMP(B)7} 18H] alfeha JIE OREM Aeon], RMPRL AP] A eM] STO AS 2) el oA Ang LF eet. LTS] RS Ab HRS] MURS HR TIBCAUC™*) oe gee Blo] Table To]. 41 IRS ed RMP yeweS] 73+ 7b tab) Prine AE RPT §~RMP(A) 183. O8meg.ml.~h, RMP(B) 145. 99mcg.ml.-th, RMP(C) 137. 05meg.ml.th=. -SAFS} RMP 34ls} 74-7 RMP(A) 117. 25meg. ml.~"h, RMP(B) 94, 49mcg. ml.-"h, RMP(C) 111. 3omeg. mi-the] sep. RMP(B)ol4] RMP yg#ts} RMP alo} 7H ACH FTB(AUC’*) o] fraavel Be ex}6 Rifampicin 9) EeAURA) BEE WEE Vol. 14, No.3 20 eup(A) Fe (B) Ri femp: Excreted in Urine. tof 20 MPC) 18 10 0 7 02 24 4-6 8 0-8 Sampling intervals (hrs. after dose) Figure—14 Human urinary excretion of totel rifampicin afteroral administration of rifampicin solution, rifampicin 300 mg capsules and rifampicin 300mg capsules with avicel 120mg Key :[—], RMP solution; min, RMP capsules; 2992, RMP with avicel 120mg capsules,September, 1984 ea F a aA uz Figure 15—Human serum concentration of Figure 16—Human serum concentration of rifampicin after oral administra: rifampicin after oral administra- tion of rifampicin solution (cor- tion of rifampicin capsules (cor- responding to 300mg rifampicin) responding to 300mg rifampicin) Key, 0-0, RMP(A) Key : oo, RMP(A) —-, RMP(B) ==, RMPCB) —*, RMP(C) * + RMP(C) ‘Table T—Area Under the Hum: istration (correspondii Rifampicin Capsules Serum Concentration Curve (AUC) after Oral Admin- to 300mg rifampicin) by each Rifampicin Solution and RMP(A) AUC meg. mi“!.h RMP(B) AUC®S meg. ml“h RMP(C) AUC™* meg. ml. h Subjects Capsules Capsilles Caspules Solution Capsules “with " Solution Capsules “with, Solution Capsules ~ with avicel avicel a 116.77 126.96 120.99 127-43 87.99 122.14 124.07 122.96 192.64 119.43 122.11 128.47 160,98 103.11 108.96) 125.96 128.96 98.96 130.49 151.64 104.98 129.43 143.63 Jo7.24 136.44 139.14 182.38 106.17 182.96 106.11 17.64 127.92 91.99 151.96 M491 111,96 134.99 188.92 79.99 Mi 145.49 121.47 119.88 9.17 116.18 121.75 149.05 85.96 132, 129.00 103.67 144.48, mean::8.D. 133.08 117.25 123.81 5.99 94.4918, 197.05 111.30 133.56 1212 EMMA 39.26 £11.85 £10.33 £10.93 £1049 11.38 11.76 aarene| SZ 4e}yigh c=] RMP(B)S] RAY 0.6479] 31}. RMP(CB) ol 4 PHENO] A, RAS RS BH Weel) et RA Hoses] wd 2p 7% 0-712, 0.6472 A] ¥]eahgleh. RMP 4h 3 AvicelS Hing RMP 3h-d-2 AHS 3+ AS RMPS| BES Hee we Se Fig. 173} Beh. = GRE wa AvicelS wore RMP GIS 298 74 4 wil BP A AE o} RG MRS] Sees ew] 6} SAL RMP Zhe} bet —esbsted. eat RMP yi, RMP 2h 2 Avice wimg: RMP 2}4¢ sepReb F lui RMP(A) RMP(B), RMP(C)2} WES WIE (IL Fig. 183} 2ep.18 Rifampicins| AFUE] AM FATE Vol. 14, No.3 8 6 a MPA) 2 RMP(B) 2 20 18 neg Rifampicin/ml Serum pMP(C) SS eS 0 12 4 6 8 Time (hrs. after dose) Figure 18—Human serum concentration ot rifampicin arter oral administration (corresponding to 300mg rifampicin) by each rifampicin capsules, and rifampicin with Avicel 120mg capsules. Key: 0——e, RMP solution; .——-, RMP capsules; *—*, RMP with avicel 120mg capsulesSeptember, 1984 + aA et a a 9 Figure 17—Human serum concentration of rifa~ mpicin? after ‘oral administration (corresponding to 300mg rifampicin) by each rifampicin capsules with avicel 120mg Key : 02, RMP(A) ; - — +, RMP(B); ++, RMP(C) Fig. 18 4" RMP(A)= RMP iako] 4] QS] Eo} stacey = al Sl AvicelS Hina RMP Abdo] eh Apel ASMA este. EG RMP(B)E RMP Vio] A 1H AL-Foll ste MEMES) Sebspohewl, RMP Zh BS Avicel& We RMP Yel +] 4h Fo} Rh MILE Eset sieh. Wal RMP(C)= RMP sifeol| Ad 2m Lol AGLI] Se sL ee] RMP ad oy Avicel$ ing RMP lol} anit) 3-0) HRMS] Ee} (Table H). S| RE Bed Avicels} yim7+ RMP(B)ol2} 94. 49meg.ml.~'he] 4] 125. 35mceg. ml. ~*h 2 AMM SE yebsis. ZebolAe SrAlae APE wolFRS Be HAA BIR © 4+ UR. sens Avicelsl RM} 2 abel] WAS Ale Shae. MUP PREC AIRIBES = Sees) we) RMPCB)o| igh HRA SHE deka lhe AS Sve AVS MOlsSLS BWR BU LE + glel HLM] S7t9} Hts AEM FALS] BMALAS Ao + wae. & a QULA SATS ofS MRM A WEUELLA rifampicin(C)7t Pe PE HAS Yebaists. 2 HAAS MSA Ab zal MMT rifampicin(B)z}7}ASe] Wills|sla Avicels} ont 7} eel} an WHMIS S7}4|tlov] 2 $ AvicelS inet rifampicin (B)7k 7} be] yell s]shep. 3. RE PLR WERE rifampicin Yas] 44 rifampicin(A), rifampicin(B) rifampcinie(C) 25 »|%% relative systemic availabilityS Uepujgest Avicel wins] 74 rifampicin(A), rifampicin(B)o] 4 RF PHI oblate rifampicin(C)eiz 2 »lalz] Seket. gherk iis rifampicin wee vite P Bene ARF MTGRCAUC*) 0.2. ¥ca}el rifampicin yo} go]4] rifampicin(A)+rifampicin(C)> rifampicin(B)s] Ee]120 Rifampicing) 21AUBaR BAR FE Vol. 14, No.3 Qs Avicele Km rifampicin Boye ANAS Zs AUC] SH BRS Bat 2] °]% rifampicin(B)7} AERA Sheba. x ® 1) P, Sensi, P. Margalith, and M.T. Timbal, 11 Farmaco, Ed. Sci) M, 146(1959). 2) S, Riva, et al, Rifamyein: General Review. 3) P. Seusi, N. 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