DUOC HO. fan mil'si(j ^Mi/di/ ^tl/iis t^isso (I)lit Glas 11 ' ' SO 499 * NAM THl> 57 * THANG RA 1 KY * ISSN BO Y T XUAT BAN

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1 fan cm 2017 DUOC HO SO 499 * NAM THl> 57 * THANG RA 1 KY * ISSN mil'si(j ^Mi/di/ ^tl/iis t^isso (I)lit Glas 11 ' ' BO Y T XUAT BAN TCDH Dja chi Toa soan: 138A Giang V6 - Quan Ba Dinh - Ha Noi Tel:

2 TAP CHI Dime HOC ISSN /2017 (So 499 NAM 57) PHARMACEUTICAL JOURNAL ISSN /2017 (N 499 Vol. 57) MUC LUC CONTENTS TONG QUAN PHUNG THANH HUONG, PHAM THUY LINH, NGUYEN TH! MAI HUONG, NGUYEN THANH HUYEN: Tong quan ve dung thuoc theo ca the trong dieu trj ung thir 3 TRAN TRONG BlEN, VU MAI HUONG, BUI TH THUY LUYEN, NGUYEN VAN HAN: Nhya trao doi ion va cac tiem nang irng dung trong Y Dirge hoc 7 NGHlEN CITU - KY THUAT PHAM THj THUY VAN, l_ TH! HUONG GIANG, PHAM CAM PHUONG: Phan tich tinh hinh sir dung va tac dung khong mong muon cua sorafenib trong dieu tri ung thir bieu mo te bao gan tai Trung tarn Y hoc hat nhan va Ung bircru, Benh vien Bach Mai 13 DANG TH! CHUNG THUY, TR NH HOANG DUONG, HA DIEU LY, NGUYEN OUC TUAN: Phan tich vlt piperacillin trong moi trirong san xuat cua nha may san xuat khang sinh piperacillin 17 NGUYEN TH! THANH MAI, TRAN BAO TRAM, TRUONG TH CHlEN, NGUYEN TH HlEN, NGUYEN TH! HA LY, PHUONG THEN THUONG: Danh gia kha nang sinh hoat chat cordycepin cua mot so giong Cordyceps militaris trong len men chim 22 NGUYEN HOANG TUAN, NGUYEN THj TUOI, NGUYEN THANH TUNG: Dac diem vi hoc va xac dinh ham lirgng diosgenin cua than rl cay ran trau thu hai tai Da Nang 25 TRUONG PHUONG, TRAN NGQC HOANG DUNG: Nghien ciru dieu che benfotiamin 30 PHAM TH THUY VAN, DUONG TH THANH: Tac dong cua cac can thiep dirge lam sang tren ke don khang sinh nhom carbapenem tai mot benh vien da khoa tuyen tinh 35 NGUYEN TUNG SON, NGUYEN DUY TAN, NGUYEN MAI HOA, VO TH THANH BINH, NGUYEN HOANG ANH: Phan tich tinh hinh sir dung thuoc khang nim dg phong tren benh nhan ghep te bao g6c tai Vien Huyet hoc - Truyen mau Trung irong 39 HUYNH NGOC TRINH, L THI HOAl THAO, HUYNH THj NGOC PHUONG: Ctng dung phan irng Ellman trong danh gia hoat tinh khang acetylcholinesterase in vitro cua mot so dan chat hydrazon va mu6i pyridinium cua hydrazon 42 OVERVIEW PHUNG THANH HUONG, PHAM THUY LINH, NGUYEN TH! MAI HUONG, NGUYEN THANH HUYEN: Review on personalized medication or medicine in cancer treatment 3 TRAN TRONG BIEN, VU MAI HUONG, BUI THj THUY LUYEN, NGUYEN VAN HAN: Ion exchange resins and application potential to medicine and medical care 7 RESEARCH - TECHNIQUES PHAM TH THUY VAN, L TH HUONG GIANG, PHAM CAM PHUONG: Study on actual use of the sorafenib for treatment hepatocellular carcinoma at The Nuclear Medicine and Oncology Center - Bach Mai Hospital 13 DANG TH CHUNG THUY, TRjNH HOANG DUONG, HA DIEU LY, NGUYEN DUC TUAN: Tracing analysis of piperacillin in the working environments of pharmaceutical factories manufacturing piperacillin preparations 17 NGUYEN TH THANH MAI, TRAN BAO TRAM, TRUONG TH CHEN, NGUYEN TH HlEN, NGUYEN TH! HA LY, PHUONG THEN THUONG: Cordycepin productivity of Cordyceps militaris trains grown by submerged culture 22 NGUYEN HOANG TUAN, NGUYEN TH! TUOI, NGUYEN THANH TUNG: Microscopic characterization and diosgenin content of the rhizomes of Dioscorea dissimulans Prain & Burkill collected at Da Nang province 25 TRUONG PHUONG, TRAN NGOC HOANG DUNG: Study on synthesis of benfotiamine 30 PHAM TH THUY VAN, DUONG THI THANH: Effects of clinical pharmacists's interventions on prescription of antibiotics of carbapenem group at a provincial central hospital 35 NGUYEN TUNG SON, NGUYEN DUY TAN, NGUYEN MAI HOA, VO TH THANH BlNH, NGUYEN HOANG ANH: Critic analysis of the use of antifungal prophylaxis for hematopoietic stem cell transplantation recipients in National Institute of Hematology and Blood Transfusion 39 HUYNH NGOC TRINH, LE TH HOAl THAO, HUYNH TH NGOC PHUONG: The use of Ellman reaction in estimation of in vitro antiacetylcholinesterase activity of some hydrazone derivatives and pyridinium salt of hydrazone 42

3 Muc luc LE BlNH CHI, TRAN NGQC HANG, NGUYEN TH ANH HU&NG, PHAM TH NGOC MAI: Xac dinh amlopidin va perindopril blng dien di mao quan 47 NGUYEN TH! NGOC YEN, DUONG DiNH CHUNG, BUI HONG QUAN, TRAN CAT DONG, NGUYEN VAN THANH: Toi iru hoa moi trirang len men Saccharomyces boulardii sir dung ma tran Plackett- Burman va phirong phap dap img be mat - thiet ke cau true co tarn 49 NGUYEN QUOC VUONG, NGUYEN THUY DUONG: Danh gia hoat tinh theo hirong ire che mien dich in vitro va in vivo cua auronol glucosid alphitonin d glucopyranosid 51 TRINH TUY AN, HUYNH NGOC THUY: Sang loc in vitro, in vivo tac dung ha acid uric mau cua mot so dirge lieu thu hai tai cac tinh phfa Nam Viet Nam 53 L TH! LOAN, HA VAN OANH, DO THj HA, CHU TH THANH HUYEN, LE Vl T DUNG: Nghien cim dac diem thgc vat cay bac thau (Argyreia acuta Lour.), ho Khoai lang (Convolvulaceae) 58 NGUYEN HUY KHIEM, TA MANH CUONG, PHAM TH THUY VAN: Phan tich tinh hinh sir dung khang sinh tren benh nhan tho may 62 DANG KIM THU, NGUYEN THj KIM THU, BUI THANH TUNG: Tac dung ire che enzym xanthin oxidase va ha acid uric mau cua dich chiet la tia to (Perilla frutescens L.) 65 NGUYEN TH! TRANG OAl, HUYNH NGOC THUY: Nghien ciru hoat tinh khang viem tir than cay bim bjp (Clinacanthus nutans (Burm. f.) Lindau, Acanthaceae) 68 NGUYEN MINH LUYEN, HOANG TH! Dl U HUONG, HA VAN OANH, LE Vl T DUNG, DAO TH THANH HlEN: Nghien ciru dac diem thirc vat va so bo thanh phan hoa hoc cay nhirong le kirn cang (Myxopyrum smilacifolium (Wall.) Blume, hp Nhai (Oleaceae)) 70 PHAM THANH MANH, NGUYEN VAN Ll U, DO VAN BlNH, NGUYEN VAN THU, HOANG Vl T DUNG: Phan lap hai hop chit oligomer resveratrol tir re cay lac (Arachis hypogaea L., hp Oau - Fabaceae) 73 NGUYEN PHUC DAM, THAI TH! TUYET NHUNG, PHAM THUA NGHIER NGUYEN TH NGOC VAN, NGUYEN TH! THU TRAM: SO bo khao sat hoat tinh khang vi sinh vat va thanh phan hoa hoc cua day vac (Cayratia trifolia (L.) Domin, ho Nho - Vitaceae) 76 VU DUC LOI, NGUYEN THI. KIM THU: Ba hop chat flavonoid phan lap tir la cay dau tlm (Morus alba L.) thu hai tai tinh Thai Nguyen 79 TRAN NHU NGUYEN, TRAN THI. PHUONG UYEN, TRUONG CONG TR, DO TH HONG TUOI: Xay dirng mo hinh ung tho gan tren chuot nhlt blng te bao HepG2 va khao sat tac dong khang ung tho cua che pham liposom paclitaxel 82 LE DlNH CHI, TRAN NGOC HANG, NGUYEN THj ANH HUO'NG, PHAM THj NGQC MAI: Determination of amlopidine and perindopril by capillary electrophoresis 47 NGUYEN TH! NGOC YEN, DUONG BINH CHUNG, BUI HONG QUAN, TRAN CAT DONG, NGUYEN VAN THANH: Optimization of fermentation medium for the probiotic bacterium Saccharomyces boulardii using plackett-burman design and response surface methodology applied central composite design 49 NGUYEN QUOC VUONG, NGUYEN THOY DUONG: Immunosuppressive property in vitro and in vivo of auronol glucoside alphitonin-4-o-p-d glucopyranoside 51 TRjNH TUY AN, HUYNH NGOC THUY: Screening some medicinal plants grown in the South Vietnam for the reduction of the blood uric acid level 53 LE TH! LOAN, HA VAN OANH, DO TH! HA, CHU TH! THANH HUYEN, LE Vl T DUNG: Study on the botanic characterization of the plant "bac thau" (Argyreia acuta Lour., Convolvulaceae) 58 NGUYEN HUY KHlEM, TA MANH CUONG, PHAM TH! THUY VAN: The actual antibiotics used for the patient in mechanical ventilation-breathing 62 DANG KIM THU, NGUYEN THI KIM THU, BUI THANH TUNG: Inhibitory activity on and the xanthine oxidase enzyme and hypouricemic effect of the leaf extracts from Perilla frutescens L. 65 NGUYEN TH! TRANG OAl, HUYNH NGOC THl)Y: Study on the inflammatory activity of the stem extracts of the plant Clinacanthus nutans (Burm. f.) Lindau, (Acanthaceae) 68 NGUYEN MINH LUYEN, HOANG TH! Dl U HUONG, HAVAN OANH, LE VlETDUNG, DAOTHj THANH HlEN: Detailed botanic characterization and preliminary phytochemical study on the "nhirong le kirn cang" (Myxopyrum smilacifolium (Wall.) Blume, (Oleaceae)) 70 PHAM THANH MANH, NGUYEN VAN Ll U, DO VAN BlNH, NGUYEN VAN THU, HOANG Vl T DUNG: Isolation of oligomer resveratrol compounds from the roots of the groundnut (Arachis hypogaea L., Fabaceae) 73 NGUYEN PHUC DAM, THAI TH! TUYET NHUNG, PHAM THUA NGHIEP, NGUYEN TH! NGOC VAN, NGUYEN TH! THU TRAM: Preliminary study on antimicrobial activity and natural compounds of Cayratia trifolia (L.) Domin, Vitaceae 76 VU DUC LOI, NGUYEN TH KIM THU: Isolation of three flavonoids from the Morus alba L. growing in Thai Nguyen province 79 TRAN NHU NGUYEN, TRAN TH PHUONG UYEN, TRUONG CONG TRj, DO TH HONG TUOI: The model of HepG2 cell line-induced hepatic tumour in mice for evaluation of anti-cancer power of the paclitaxel liposome preparation 82 TAP CHI DlTOC HOC -11/2017 (SO 499 NAM 57)

4 Nghien CLFU - Ky thuat cua dirge st a hai khoa la khac nhau. 0 Khoa Ngoai tieu hoa, viec thieu thai gian trao doi tare tiep giira bac sy va dirge st lam sang (thirdng trao doi qua dien thoai hoac qua giay nhln) gay kho khan trong tao dung moi quan he thau hieu va chia se giira hai ben. Day co le nguyen nhan chinh khien cho nhcrng tac dgng de xuat cua dirge st lam sang chira dirge chip thuan nhieu d Khoa Ngoai tieu hoa. Tai Khoa HSNK, khi dirge st lam sang hoat dgng tai khoa, cac bac sy rat vui ve va thang than trao doi vdi dirge st lam sang nhieu van de trong dieu tri. Do vay, nhom nghien ciru nhan dinh can thiep dirge lam sang tao dirge nhcrng thay doi va hieu qua nhat dinh trong thgc te dieu trj mac du nhieu chl tieu nha so lirgng DRP trung binh, ty le benh nhan dung carbapenem sau khi co can thiep giam chira co y nghta thong ke, co the do thai gian nghien cdu chaa dai, cd miu con nhd. Cac can thiep ve Iga chpn thuoc dirge chap nhan vdi ty le 55-57%, tuy nhien hieu qua cua can thiep tren viec giam DRP ve Iga chpn thuoc lai chira the hien ro rang, dac biet d Khoa Ngoai tieu hoa. Ly do co the la sd lirgng benh nhan sir dung khang sinh carbapenem tang manh trong giai doan nay va, do thieu nhan Igc, hoat dpng xem xet sir dung thuoc cua dirge st khdng dirge tidn hanh tren tat ca cac benh nhan, thieu thai gian tirang tac vdi bac sy. Trong cac can thiep, can thiep ve lieu dung, each dung nhan dirge sg ung hp tich cgc tir phi'a bac st vdi ty le cao nhat (75 va 100% d HSNK va 66,7 va 100% d Ngoai tieu hda), co le do day la nhcrng can thiep co can cd xac djnh ro rang va kha nang thgc hien cao. Hieu qua cua cac bien phap can thiep ve lieu dung, each dung dirge the hien kha ro rang, giam DRP ve each dung cd y nghta thong ke. Ket luan Vdi nghien cdu ban dau tren mot qui mo nho, can thiep cua dirge st lam sang da giup giam thieu cac vln de lien quan den thuoc, so lirgng va chi phi sir dung khang sinh carbapenem tai hai khoa he ngoai cua mot benh vien da khoa tuyen tinh. Cac dirge st co the then khai cac mo hinh hoat dpng tren cac ITnh vgc khac de toi iru hda sir dung thuoc cho benh nhan. Tai lieu tham khao 1. Lima A. L, Oliveira P. R., et al., (2011). "Carbapenem stewardship: positive impact on hospital ecology", Braz J. Infect Dis., 15(1), pp Livermore D. M., Sefton A. M. et al. (2003), "Properties and potential of ertapenem", J. Antimicrob. Chemother., 52(3), pp Lucca J. M., Ramesh M. et al. (2012), "Impact of clinical pharmacist interventions on the cost of drug therapy in intensive care units of a tertiary care teaching hospital", J. Pharmacol. Pharmacother, 3(3), pp Molino Cde G., Carnevale R. C. et al. (2014), "Impact of pharmacist interventions on drug-related problems and laboratory markers in outpatients with human immunodeficiency virus infection", Ther. Clin. Risk Manag., 10, pp Naivalulevu L. (1990), "Training for rational drug use", ARI News, 18, Shah P. M. (2008), "Parenteral carbapenems", Clin. Microbiol. Infect, 14 Suppl 1, pp Van Mil Foppe (2005), "Drug related problems: A cornerstone for pharmaceutical care", J. Malta Pharm. Pract, (Ngay nhan bai: 19/09/ Ngay phan bien: 27/09/ Ngay duyet dang: 20/10/2017) Phan tich tinh hinh su* dung thuoc khang nam dy phong r r tren benh nhan ghep te bao goc tai Vien Huyet hoc - Truyen mau Trung irotig r Nguyen Tung Son 1, Nguyen Duy Tan 2, Nguyen Mai Hoa 1 V6 Th Thanh Binh 3, Nguyen Hoang Anh 1 * 'Trung tarn DI & ADR Quoc gia, Truong Dai hoc Duac Ha Noi 2 Khoa Duqc, Vien Huyet hoc - Truyen mau Trung uang 3 Khoa Ghep te bao gdc, Vien Huyet hoc - Truyen mau Trung ucmg ' anh90tk@yahoo.com Summary Characteristics of the pattern of use of antifungal prophylaxis in hematopoietic stem cell transplantation (HSCT) recipients were studied for detailed description. Adult HSCT recipients without using antifungal treatment were recruited from start of stem cell transfusion in Vietnam National Institute of Hematology and Blood Transfusion (from April to December 2016) to the end of antifungal prophylaxis or start of antifungal treatment. Appropriateness was defined based on National Comprehensive Cancer Network (NCCN) guidelines. Clinically significant dmg-drug interactions related to antifungals were defined based on Hansten and Horn's Drug interaction and management The study involved 38 patients (mean age: 35.7 ± 12.0; 57.9% male), all were admitted, included 21 autologous and 17 allogenic HSCT recipients. Azoles prophylaxis was given to r TAP CHI DUOC HOC - 11/2017 (SO 499 NAM 57) 39

5 Nghien CLFU - Ky thuat 100% of patients with median 17.5 days ( ), fluconazole as an antifungal agent of the most use to 94.7% of patients and in 74.5% of episodes. Indication was appropriate in 44.7% - 0% in autologous and 100% in allogeneic group. In patients with appropriate indication, choice of antifungal agents was 100% appropriate. 100% of patients used inappropriate dosage, mostly lower than the recommeded dosage with azoles. 12.7% had appropriate prophylactic time. Potential drug-drug interactions were identified in 92.1% of patients. Most frequent interactions involved azoles-diazepam (80.4% of episodes) and azoles-immunosuppressive drugs (49% of episodes). In conclusion, a considerably high proportion of non-adherence of antifungal prophylaxis guidelines was revealed, that seemingly called for an adequate programme for antifungal stewardship to strengthen rational use of antifungal in such specific circumstances. Keywords: Antifungal prophylaxis, drug use evaluation, hematopoietic stem cell transplantation. Oat van de Ghep te bao goc tao mau (Hematopoietic stem cell transplantation - HSCT) la mot ky thuat phdc tap, cd the gay ra nhieu bien chirng nghiem trpng cho benh nhan, trong do co nhiem nam m. Sir dung thuoc khang nam dg phdng tren doi tirgng benh nhan ghep te bao goc dem lai nhieu Igi fch, tuy nhien, viec sir dung khdng hgp ly cac thuoc nay lam tang chi phi dieu trj cho benh nhan, tang xuat hien cac chung vi nam khang thuoc cung nhir tang nguy ca xuat hien tac dung khdng mong muon do thuoc khang nam hoac do hau qua cua tirang tac cd lien quan den thuoc khang nam M. Khoa Ghep te bao goc, Vien Huyet hoc - Truyen mau Trung irang la ca sd dau nganh trong ITnh vgc ghep te bao goc tai Viet Nam. Day cung la nai co ty le nhiem nam cao, chiem 40,9% so benh pham nam toan Vien, dong thai, Khoa Vi sinh cua Vien cung da ghi nhan hien tirgng giam nhay cam cua Candida tropicalis vdi fluconazol Pl. Tren ca sd do, chung tdi tien hanh de tai nay vdi muc tieu phan tich phac do dg phdng blng thuoc khang nam tren benh nhan ghep te bao goc, tir do, de xuat dirge cac bien phap gdp phan nang cao hieu qua sir dung thuoc khang nam cua Vien. Doi tirgng va phirong phap Doi tirgng nghien ciru: Toan bp benh nhan dirge tien hanh HSCT tai Khoa Ghep te bao goc, Vien Huyet hoc - Truyen mau Trung irang tir ngay 01/4/2016 den ngay 31/12/2016; loai tnr benh nhan cd tuoi < 18 tuoi va benh nhan dang sir dung phac do dieu tri khang nam tai thai diem ghep. Phiromg phap nghien cu>u: Nghien ciru mo ta, khdng can thiep, theo ddi doc tien ciru. Moi benh nhan dirge theo ddi va ghi lai thong tin bat dau tir ngay ghep tdi thai diem benh nhan ngirng sir dung thuoc khang nam, benh nhan chuyen sang phac dd dieu tri khang nam, benh nhan tir vong hoac chuyen hoi sire tfch cgc. Bp tieu chi danh gia dirge nhdm nghien ciru xay dgng dga tren hirdng dan cua Mang lirdi Ung thir Quoc gia Hoa Ky (National Comprehensive Cancer Network - NCCN) phien ban w va Rieng cac tieu chf ve lieu dung cua voriconazol va fluconazol trong dg phdng khang nam dirge tham khao tir td thong tin san pham dirge phe duyet tai Anh [6) do khdng dirge de cap trong Hirdng dan cua NCCN. Tirang tac lien quan din thuoc khang nam dirge xac djnh dga tren cudn Hansten and Horn's Drug Interaction Analysis and Management 2013 va Iga chpn cac tirang tac tir mire dp 3 trd len m. Trong bp tieu chf, tieu chf chi djnh thuoc khang nam dirge tinh theo so benh nhan, con tieu chf Iga chpn thuoc, lieu dung, dirdng dung cua cac thuoc nay dirge tinh theo so dgt dieu tri (tire la khoang thai gian tinh tir luc bit dau den luc ket thuc sir dung mot thuoc khang nam vdi muc dfch dg phdng). Ngoai ra, tieu chf Iga chpn thuoc khang nam chf xet tren benh nhan cd chi dinh phu hgp va tieu chf ve thai gian dg phdng khang nam chi tfnh tren so benh nhan khdng tir vong, chuyen hoi sire tfch cgc hoac nhilm nlm trong qua trinh dieu trj. Xir ly so lieu: So lieu dirac xir ly bang Microsoft Excel 2016 va SPSS Ket qua Dac diem cua benh nhan HSCT trong miu nghien cim Dac diem cua benh nhan HSCT trong miu nghien ciru dirge mo ta d bang 1, hinh 1 va hinh 2. Bang 1. Dac diem nhan khiu hoc cua benh nhan trong nghien cuv Chi tieu nghien ciru Ghep to than Ghep dong loai Toan bp miu So benh nhan theo doi (%) 21/38(55,3%) 17/38(44,7%) 38/38(100%) Tudi (nam - trung binh ± SD) 36,6 + 13,5 34,7 + 10,3 35,7 ±12,0 Tuoi nhd nhat - Ion nhat So benh nhan nam (%) 11/21(52,4%) 11/17(64,7%) 22/38(57,9%) Trong mau nghien ciru, so benh nhan ghep tg than nhieu han so benh nhan ghep dong loai. Dp tuoi cua benh nhan trong miu nghien ciru phan bo rpng (18-65), nhdm benh nhan ghep tg than cd dp tuoi cao han (19-65) nhdm benh nhan ghep dong loai (18-52). Benh nhan nam cd ty le cao han trong mlu nghien ciru. Da so cac benh nhan khdng ghi nhan tien sir va benh mac kern (81,6%). Tat ca benh nhan gap bien co sau ghep deu nam trong nhdm ghep dong loai. DS tftnt nhilm nam 2.6% Dang nhiem khuan niem mac miena 2.6% Suy giam chiic nang than 5.3% Hinh 1. Tien sir cua benh nhan trong nghien cuv 40 TAP CHI DUOC HOC -11/2017 (SO 499 NAM 57)

6 Nghien ccm - Ky thuat 100% of patients with median 17.5 days ( ), fluconazole as an antifungal agent of the most use to 94.7% of patients and in 74.5% of episodes. Indication was appropriate in 44.7%-0% in autologous and 100% in allogeneic group. In patients with appropriate indication, choice of antifungal agents was 100% appropriate. 100% of patients used inappropriate dosage, mostly lower than the recommeded dosage with azoles. 12.7% had appropriate prophylactic time. Potential drug-drug interactions were identified in 92.1% of patients. Most frequent interactions involved azoles-diazepam (80.4% of episodes) and azoles-immunosuppressive drugs (49% of episodes). In conclusion, a considerably high proportion of non-adherence of antifungal prophylaxis guidelines was revealed, that seemingly called for an adequate programme for antifungal stewardship to strengthen rational use of antifungal in such specific circumstances. Keywords: Antifungal prophylaxis, drug use evaluation, hematopoietic stem cell transplantation. Oat van de Ghep te bao goc tao mau (Hematopoietic stem cell transplantation - HSCT) la mot ky thuat phire tap, cd the gay ra nhieu bien chirng nghilm trong cho benh nhan, trong dd cd nhilm nlm m. Sir dung thudc khang nam dg phdng tren doi tirgng benh nhan ghep te bao goc dem lai nhieu Igi fch, tuy nhiln, viec sir dung khdng hgp ly cac thuoc nay lam tang chi phi dieu trj cho benh nhan, tang xuat hien cac chung vi nam khang thuoc cung nhir tang nguy ccr xuat hien tac dung khdng mong muon do thuoc khang nam hoac do hau qua cua tirang tac cd lien quan din thuoc khang nam l2]. Khoa Ghep te bao goc, Vien Huyet hoc - Truyen mau Trung irang la ca sd dau nganh trong ITnh vgc ghep te bao goc tai Viet Nam. Day cung la nai cd ty II nhilm nam cao, chiem 40,9% so benh pham nam toan Vien, dong thai, Khoa Vi sinh cua Vien cung da ghi nhan hien tirgng giam nhay cam cua Candida tropicalis vdi fluconazol Pl. Tren ca sd dd, chung tdi tien hanh de tai nay vdi muc tieu phan tfch phac do dg phdng blng thuoc khang nam tren binh nhan ghlp te bao goc, tir dd, de xuat dirge cac bien phap gdp phan nang cao hieu qua sir dung thudc khang nam cua Vi n. Doi tirgng va phircrng phap Doi tirgng nghien cu>u: Toan bo b nh nhan dirge tiln hanh HSCT tai Khoa Ghep te bao goc, Vi n Huyet hoc - Truyln mau Trung irang tir ngay 01/4/2016 den ngay 31/12/2016; loai trir b nh nhan cd tuoi < 18 tuoi va b nh nhan dang sir dung phac do dilu trj khang nam tai thai diem ghep. Phaang phap nghien cini: Nghiln ciru ml ta, khdng can thiep, theo ddi dgc tien ciru. Moi b nh nhan dirge theo ddi va ghi lai thong tin bat dau tir ngay ghep tdi thai dilm b nh nhan ngirng sir dung thuoc khang nam, b nh nhan chuyen sang phac do dilu trj khang nam, b nh nhan tir vong hoac chuyen hoi sire tfch cgc. Bp tilu chf danh gia dirge nhdm nghiln ciru xay dgng dga trln hirdng dan cua Mang lirdi Ung thir Quoc gia Hoa Ky (National Comprehensive Cancer Network - NCCN) phien ban M va w. Rieng cac tieu chf ve lieu dung cua voriconazol va fluconazol trong dg phdng khang nam dirge tham khao tir td thong tin san pham dirge phe duy t tai Anh [6) do khdng dirge dl cap trong Hirdng dan cua NCCN. Tirang tac lien quan din thuoc khang nlm dirge xac djnh dga tren cuon Hansten and Horn's Drug Interaction Analysis and Management 2013 va Iga chpn cac tirang tac tir mde dp 3 trd lln m. Trong bo tieu chf, tieu chf chf dinh thuoc khang nam dirge tfnh theo so benh nhan, con tieu chf Iga chpn thuoc, lieu dung, dirdng diing cua cac thuoc nay dirge tfnh theo so dgt dilu trj (tire la khoang thai gian tfnh tir luc bat dau den luc kit thuc sir dung mot thuoc khang nam vdi muc dfch dg phdng). Ngoai ra, tieu chf Iga chpn thuoc khang nam chf xlt trln b nh nhan cd chi djnh phu hgp va tilu chf vl thai gian dg phdng khang nam chi tfnh trln so b nh nhan khdng tir vong, chuyln hoi sire tfch cgc hoac nhilm nlm trong qua trinh dieu trj. Xir ly so lieu: So lieu dirac xir ly bang Microsoft Excel 2016 va SPSS Ket qua Dac diem cua benh nhan HSCT trong mau nghien cu>u Dac diem cua b nh nhan HSCT trong miu nghiln ciru dirge mo ta d bang 1, hinh 1 va hinh 2. Bang 1. Dac diim nhan khau hoc cua benh nhan trong nghien cuv Chi tieu nghien cuv Gheptothan Ghep dong loai Toan bp mau So benh nhan theo ddi (%) 21/38 (55,3%) 17/38 (44,7%) 38/38 (100%) Tuoi (nam - trung binh ± SD) 36,6 ±13,5 34,7 ±10,3 35,7 ±12,0 Tuoinhd nhat-ion nhat So benh nhan nam (%) 11/21(52,4%) 11/17(64,7%) 22/38(57,9%) Trong mau nghiln ciru, so b nh nhan ghep tg than nhieu han so b nh nhan ghep dong loai. Dp tuoi cua b nh nhan trong mau nghien ciru phan bo rpng (18-65), nhdm b nh nhan ghep tg than cd dp tuoi cao han (19-65) nhdm b nh nhan ghep dong loai (18-52). B nh nhan nam cd ty l cao han trong mau nghiln ciru. Da so cac b nh nhan khdng ghi nhan tien sir va b nh mlc kem (81,6%). Tat ca b nh nhan gap bien co sau ghep deu nam trong nhdm ghep dong loai. Da time nhiem Dang nhiem khuan niem mac miens 2.6% Suy giam chiic nangthan 5.3% Viem gan B 7.9% Hinh 1. 77en scrcua benh nhan trong nghien ciiv 40 TAP CHI DUCfC HOC -11/2017 (SO 499 NAM 57)

7 Nghien cfru - Ky thuat x Ghep tv than Ghep dong loai Toan bo mau B Nhiem nam H Tu vong 12 Chuyen ICU O Hoan thanh dieu tri Hinh 2. Bien co sau ghep cua benh nhan trong nghien cuv Dac nlm dg phong diem lien quan den chi dinh thuoc khang Bang 2. Dac diim lien quan den chi dinh thuoc khang nam dg phdng Chi tieu nghien ciru Gheptothan Ghep dong loai Toan bp mau S6 benh nhan dir phdng 21/21 (100,0%) 17/17(100,0%) 38/38 (100,0%) nam(%) Thdi gian diing 16(13-17) 62(31-73) 17,5 (13-47,5) (ngay-trung vivalqr) Sd luvng va ty le sir dung thuoc (%) Fluconazol 20/21 (95,2%) 16/17(94,1%) 36/38 (94,7%) Itraconazol 2/21 (9,5%) 2/17(11,8%) 4/38(10,5%) Voriconazol 0/21 (0,0%) 4/17(23,5%) 4/38(10,5%) Posaconazol 0/21 (0,0%) 4/17(23,5%) 4/38(10,5%) % so benh nhan ghep deu dirge dg phdng bang thuoc khang nam azol. Thudc dggc sir dung nhieu nhlt la fluconazol (36 benh nhan, chiem 94,7%). Posaconazol va voriconazol chi dirge sir dung d benh nhan ghep dong loai. Ket qua phan tich phac do khang nam dg phong va lieu dung thgc te tren benh nhan so vdi lieu khuyen cao Bang 3. Ket qua phan tich phac dd khang nam dir phdng Tieu chi Ghep to than Ghep dong loai Toan bp mau Chi dinh phu hop 0/21 (0,0%) 17/17(100,0%) 17/38(44,7%) Lira chon phu hop Lidu, dudng dung phu hop Thoi gian dung phii hop 0/0 (Khong danh gia) 29/29(100,0%) 29/29(100,0%) 0/22 (0,0%) 0/29 (0,0%) 0/51 (0,0%) 0/21 (0,0%) 4/12 (33,3%) 4/33(12,1%) Tieu chi ve Iga chgn thuoc khang nam dat ty le phu hgp cao nhat, cac tieu chi con lai deu co ty le phu hgp rat thap. Nhin chung, ty le phu hgp d nhdm benh nhan ghep tg than thap han nhdm benh nhan ghep dong loai. Dae biet, ve lieu dung va dirdng dung, tat ca benh nhan deu dirge sir dung thuoc khang nam phu hgp ve dirdng dung nhirng lieu dung thgc te cua cac thuoc nay deu thap han lieu dirge khuyen cao. Cu the, lieu dung cua benh nhan dirge trinh bay trong bang 4. Cla > 50ml/phut CICr < 50 ml/phut Bang 4. Lidu dung thirc te tren benh nhan so v&i lidu khuyen cao Lieu thirc te Ghep to than (So dot didu tri) Ghep dong loai (So dot dieu tri) Fluconazol 300 mg/ngay mg/ngay mg/ngay 0 1 khdng toe mau 150 mg/ngay 1 0 Lieu khuyen cao 400 mg/ngay 200 mg/ngay Itraconazol 200 mg/ngay mg/ngay Voriconazol Bdnh nhan > 40 kg 200 mg*2 Idn/ngay 0 4 Ngay dau: 400 mg x 2 Idn/ngay. Duy tri: 200 mg * 2 lan/ngay Posaconazol 200 mg*2 Idn/ngay mg x 3 lan/ngay Dac diem tircrng tac thuoc co y nghta lam sang lien quan den thuoc khang nam Bang 5. Dac diem tuung tac thudc cd y nghta lam sang lien quan den thudc khang ndm Chi tieu nghien ciru S6dptdieutricdtuungtac(%) 20/22(90,9%) 27/29(93,1%) 47/51 (92,2%) Trung binh trong 01 dot didu tri 1,15 1,85 1,55 Cac cap tirong tac Tirang tac lien quan den thuoc khang nam dirge ghi nhan trong mau nghien ciru vdi ty le rat cao, vdi 92,1% benh nhan gap it nhat 1 tirang tac. Tirang tac pho bien nhdt la gicfa cac azol vdi diazepam, gap d 80,4% so dgt diiu tri cua benh nhan. Tirang tac gicra cac azol vdi cac Gheptothan Ghep dong loai Toan bp mau Azol 1 - diazepam 20 (90,9%) 21 (72,4%) 41 (80,4%) Azol 1 - thuoc dc che mien dich 2 0(0%) 25 (86,2%) 25 (49%) Azol 3 - omeprazol 2(9,1%) 3(10,3%) 5 (9,8%) Voriconazol - omeprazol 0 (0%) 1 (3,4%) 1 (2%) Itraconazol - methylprednisolon 1 (4,5%) 0 (0%) 1 (2%) Ghi chii: 'Fluconazol, itraconazol, voriconazol, posaconazol 2 Ciclosporin, tacrolimusritraconazol,posaconazol thuoc ire che mien djch (ciclosporin va tacrolimus) cung dirge phat hien trong 25 dgt dieu trj, chiem 49,0%. Ban luan Ket qua cua nghien ciru cho thay, dg phong bang thuoc khang nam dirge chi dinh tren toan bp benh nhan tham gia nghien ciru. Tuy nhien, chi co 17/38 chi djnh (chiem 44,7%) la phu hgp. Didu nay xuat phat tir viec benh nhan ghep tg than khong cd bieu hien viem niem mac van dirge chi djnh thuoc khang nam khdng can thiet. Tinh trang tren cung dirge ghi nhan (Xem tiep trang 46) TAP CHI DlTCfC HOC - 11/2017 (SO 499 NAM 57) 41

8 Nghien ci>u - Ky thuat 6. Rhee I. K. etal. (2001), "Screening for acetylcholinesterase inhibitors from Amaryllidaceae using silica gel thin-layer chromatography in combination with bioactivity staining", J. of Chromatography A, 915(1-2), Schneider L. S. (2000), "A critical review of cholinesterase inhibitors as a treatment modality in Alzheimer's disease", Dialogues Clin. Neurosci., 2(2), (Ngay nhan bai: 21/07/ Ngay phan bien: 24/09/ Ngay duyet dang: 20/10/2017) Phan tich tinh hinh... (TH p theo trang 41) trong nghien cdu cua Vazin va CS. theo doi trong s6 67 benh nhan sir dung fluconazol, co 19,4% dirge chi djnh khong phu hgp tren benh nhan ghep tg than khong co viem niem mac [8!. Tinh trang nay co the xuat phat tir khd khan trong viec quydt djnh chi djnh thuoc cho benh nhan ghep tg than khi chira co cdng cu nao cho phep dg doln trinh trang viem niem mac va giam bach clu trung tinh. Toan bd benh nhan trong miu nghien cdu dirge dg phong bang cac thuoc khang nam nhdm azol. Trong do, fluconazol la thuoc dirge sir dung phd bien nhat. Tuy nhien, fluconazol cung ddng dau trong cac thuoc dirge chi djnh khong phu hgp, vdi ly do da dirge de cap d phan chi djnh chira hgp ly d tren. Han naa, khong co benh nhan nao dirge sir dung fluconazol vdi lieu phu hgp. Hien tirgng tirang tg da dirge ghi nhan trong nghien cdu cua Nivoix va CS. M. Dieu nay cd the lien quan den viec d Vien chi co che pham fluconazol 150 mg vien nang va 200 mg truyen ttnh mach, trong do viec sir dung thuoc dung dirdng udng dirge sir dung pho bien va thuan tien han cho benh nhan. Sir dung fluconazol vdi lieu thap han binh thirdng co the tiem In nhieu nguy ca. Dac biet la khi Vien dang ghi nhan tinh trang gia tang de khang vdi fluconazol cua Candida tropicalis, ty le khang thuoc nam 2015 da len tdi 44%. Trong nhdm benh nhan ghep tg than, tat ca benh nhan deu sir dung thuoc khang nam khi bach clu da trd ve mire binh thirdng. Thong thirdng, benh nhan chi dirge ngdng thudc khang nlm khi tinh trang on djnh va xult vien. VI vay, viec keo dai thuoc khang nam gay lang phi chi phi dieu trj cho benh nhan. Ngirgc lai, trong nhdm benh nhan ghep dong loai, da so benh nhan ngirng sir dung thudc tnrdc ngay thd 75 sau ghep. Dieu nay la do thai gian nam vien cua da so benh nhan ghep dong loai virgt qua tran bao hiem, nen nhcrng benh nhan co tinh trang on djnh thirdng dirge xult vien trade 75 ngay sau ghep. Khi dieu tri ngoai tru, cac benh nhan nay cung khdng sir dung thuoc khang nlm do gia thanh kha cao. Taang tie pho bien nhat ghi nhan trong miu nghien cdu la taang tic giaa clc azol va diazepam cd nguy ca Urn ting nong dp trong huyet taang cua diazepam, din den tang clc bien cd bat Igi cua thudc nha an thin qui mdc, gilm khi nang phdi hgp clc cd ddng, phln xa (thlt dieu) [7]. Vdi benh nhan HSCT, diazepam chi dagc sir dung vdi muc dich an thin, vi vay, bac st nen can nhac viec phdi hgp thudc nly vdi clc azol de han chd tic dung bat Igi cho benh nhan. Taang tic cln chu y nhlt, dong thai II taang tic dagc clnh bio trong Hadng din dieu trj cua NCCN II taang tic giira clc azol khlng nam vi clc thuoc dc che mien djch (ciclosporin, tacrolimus), cd the din den suy than trong tradng hgp khdng dagc kiem solt chit che M. Hien nay, Vien da cd nhdng bien phlp gilm sit tich cgc de gilm thieu taang tic bat Igi nly, bao gom gilm sit creatinin qua bd xet nghiem thadng quy vi djnh lagng ndng dd thuoc trong miu vdi tan suit 1 lan/tuan de kiem solt hieu qui vi ddc tinh cua clc thuoc dc che mien djch. Ket luan Ket qua cua nghien cdu cho thly thgc trang sd dung thudc khlng nam dg phdng tren benh nhan HSCT tai Vien Huyet hgc - Truyen miu Trung aang. Nghien cdu da chi ra ty le khdng phu hgp cao trong sd dung thuoc khlng nlm dg phdng d doi tagng benh nhan nly ve clc tieu chi chi djnh, lieu dung vi thai gian dung. Dieu nay cho thay cln thief then khai chaang trinh quln ly thuoc khlng nlm tai Vien nham nang cao chit lagng sd dung thudc. Tai lieu tham khao 1. DiPiro J. T, Talbert R. L. et al. (2017), Pharmacotherapy: A Pathophysiologic Approach, 10 th Edition, McGraw-Hill Education, New York, pp Andes D., Azie N. et al. (2016), "Drug-drug interaction associated with mold-active triazoles among hospitalized patients", Antimicrob. Agents Chemother., 60(6), pp Khoa Vi sinh (2015), Bao cao ve tinh hinh nhiem khuan tai Vien Huyet hoc - Truyen mau Trung uvng nam 2015, Vien Huyet hoc - Truyen mau Trung aong. 4. National Comprehensive Cancer Network (2015), Prevention and treatment of cancer-related infections (Version ), < pdf/infections.pdf> [Accessed: 03/01/2016]. 5. National Comprehensive Cancer Network (2016), Prevention and treatment of cancer-related infections (Version ), < pdf/infections.pdf> [Accessed 15/12/2016]. 6. Summary of Product Characteristics for Diflucan 200 mg Hard Capsule (fluconazole): VFEND 200 mg film-coated tablet (voriconazole) (2016), < emc>, [Accessed: 09/3/2016]. 7. Hansten P. D., Horn J. R. (2013), Hansten and horn's drug interactions analysis and management, Lippincott Williams & Wilkins, St. Louis. 8. Vazin A., Davarpanah M. A. et al. (2015), "Antifungal agent utilization evaluation in hospitalized neutropenic cancer patients at a large teaching hospital", Drug Healthc. Patient Sat, 7, pp Nivoix Y, Launoy A. et al. (2012), "Adherence to recommendations for the use of antifungal agents in a tertiary care hospital", J. Antimicrob. Chemother, 67(10), pp (Ngay nhan bai: 19/09/2017- Ngay phan bien: 28/09/2017- Ngay duyet dang: 20/10/2017) 46 TAP CHI DUOC HOC - 11/2017 (SO 499 NAM 57)