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T A P CHI Dime H O C ISSN 0866 - 7861

11/2017 (So 499 NAM 57)

P H A R M A C E U T I C A L J O U R N A L

ISSN 0866 - 7861 11/2017 (N° 499 Vol. 57)

MUC L U C C O N T E N T S

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 v l t 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 T H E N 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 r l 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 n i m 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

R E S E A R C H - 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 D U C 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| C H E N , NGUYEN TH| HlEN, NGUYEN TH! HA LY, PHUONG T H E N 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 anti-acetylcholinesterase activity of some hydrazone derivatives and pyridinium salt of hydrazone 42

• Muc luc • LE BlNH CHI, TRAN NGQC HANG, NGUYEN

TH| ANH H U & N G , PHAM TH| NGOC MAI: Xac dinh amlopidin va perindopril b l ng 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-4-0-3-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, C H U TH| THANH HUYEN, LE Vl£T DUNG: Nghien c im 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 ch i t 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: S O 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 D U C LOI, NGUYEN THI. KIM THU: Ba hop chat flavonoid phan lap tir la cay dau t l m (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 nh l t b lng 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 T H O Y 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, H A VAN OANH, DO TH! H A , 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 T H U , 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 D U C 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 T U O I : The model of HepG2 cell line-induced hepatic tumour in mice for evaluation of anti-cancer power of the paclitaxel liposome preparation 82

T A P C H I D l T O C H O C -1 1 / 2 0 1 7 ( S O 4 9 9 N A M 57)

• Nghien CLFU - Ky thuat

cua d i rge sT a hai khoa la khac nhau. 0 Khoa Ngoai tieu hoa, viec thieu tha i gian trao doi tare tiep gi ira bac sy va d i r ge sT lam sang ( th i rdng trao doi qua dien thoai hoac qua giay n h l n ) gay kho khan trong tao d u n g moi quan he thau hieu va chia se gi i ra hai ben. Day co le nguyen nhan chinh khien cho nhCrng tac dgng de xuat cua d i rge sT lam sang chi ra d i rge c h i p thuan nhieu d Khoa Ngoai tieu hoa.

Tai Khoa HSNK, khi d i rge sT lam sang hoat dgng tai khoa, cac bac sy rat vui ve va thang than trao doi vd i d i rge sT lam sang nhieu van de trong dieu tri. Do vay, nhom nghien c i ru nhan dinh can thiep d i rge lam sang tao d i rge nhCrng thay doi va hieu qua nhat dinh trong thgc te dieu trj mac du nhieu chl t ieu n h a so l i rgng DRP trung b inh, ty le benh nhan dung carbapenem sau khi co can thiep g iam ch i ra co y nghTa thong ke, co the do thai gian nghien c d u chaa dai, c d m i u con nhd.

Cac can thiep ve Iga chpn thuoc d i rge chap nhan vd i ty le 55-57%, tuy nhien hieu qua cua can thiep tren viec g iam DRP ve Iga chpn thuoc lai ch i ra the hien ro rang, dac biet d Khoa Ngoai tieu hoa. Ly do co the la sd l i rgng 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 d i rge sT khdng d i rge tidn hanh tren tat ca cac benh nhan, thieu thai gian t i rang tac vd i bac sy. Trong cac can thiep, can thiep ve lieu dung, each dung nhan d i rge s g ung hp tich c g c t ir phi'a bac sT vd i 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 c d xac djnh ro rang va kha nang thgc hien cao. Hieu qua cua cac bien phap can thiep ve lieu dung, each dung d i rge the hien kha ro rang, g iam DRP ve each dung cd y nghTa thong ke.

Ket luan Vd i nghien c d u ban dau tren mot qui mo nho, can

thiep cua d i rge sT lam sang da giup g iam thieu cac v l n de lien quan den thuoc, so l i rgng va chi phi s i r dung khang sinh carbapenem tai hai khoa he ngoai cua mot benh vien da khoa tuyen tinh. Cac d i rge sT co the then khai cac mo hinh hoat dpng tren cac ITnh v g c khac de toi i ru 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. 1-5.

2. Livermore D. M., Sefton A. M. et al. (2003), "Properties and potential of ertapenem", J. Antimicrob. Chemother., 52(3), pp. 331-344.

3. 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. 242-247.

4. 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. 631-639.

5. Naivalulevu L. (1990), "Training for rational drug use", ARI News, 18, 5.

6. Shah P. M. (2008), "Parenteral carbapenems", Clin. Microbiol. Infect, 14 Suppl 1, pp. 175-180.

7. Van Mil Foppe (2005), "Drug related problems: A cornerstone for pharmaceutical care", J. Malta Pharm. Pract, 10. 5-8.

(Ngay nhan bai: 19/09/2017 - Ngay phan bien: 27/09/2017 - Ngay duyet dang: 20/10/2017)

r r

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

Nguyen Tung Son1, Nguyen Duy Tan2 , Nguyen Mai Hoa1

V6 Th | Thanh Binh3, Nguyen Hoang Anh1* 'Trung tarn DI & ADR Quoc gia, Truong Dai hoc Duac Ha Noi

2Khoa Duqc, Vien Huyet hoc - Truyen mau Trung uang 3Khoa Ghep te bao gdc, Vien Huyet hoc - Truyen mau Trung ucmg

'E-mail: 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 2013. 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

T A P C H I D U O C H O C - 11/2017 (SO 499 N A M 57) 39

• Nghien CLFU - Ky thuat

100% of patients with median 17.5 days (13 - 47.5), 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.

Trong bp tieu chf, tieu chf chi djnh thuoc khang nam d i rge t inh theo so benh nhan, con tieu chf Iga chpn thuoc, lieu dung, d i rdng dung cua cac thuoc nay d i rge t inh theo so dg t dieu tri (tire la khoang thai gian t inh t ir luc b i t dau den luc ket thuc sir dung mot thuoc khang nam vd i muc dfch d g phdng). Ngoai ra, tieu chf Iga chpn thuoc khang

Oat v a n d e

Ghep te bao goc tao mau (Hematopoiet ic stem cell transplantation - HSCT) la mot ky thuat phdc tap, cd the gay ra nhieu bien ch i rng nghiem trpng cho benh nhan, trong do co nhiem nam m . S i r dung thuoc khang nam d g phdng tren doi t i r gng 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 c a xuat hien tac dung khdng mong muon do thuoc khang nam hoac do hau qua cua t i rang tac cd lien quan den thuoc khang nam M . Khoa Ghep te bao goc, Vien Huyet hoc - Truyen mau Trung i r ang la c a s d dau nganh trong ITnh v g c 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 tha i , Khoa Vi sinh cua Vien cung da ghi nhan hien t i rgng g iam nhay cam cua Candida tropicalis vd i f luconazol P l . Tren c a s d do, chung tdi tien hanh de tai nay vd i muc tieu phan t ich phac do d g phdng b l n g thuoc khang nam tren benh nhan ghep te bao goc, t ir do, de xuat d i rge cac bien phap gdp phan nang cao hieu qua s i r dung thuoc khang nam cua Vien.

D o i t i r g n g v a p h i r o n g p h a p

Doi t i rgng nghien c i ru : Toan bp benh nhan d i rge tien hanh HSCT tai Khoa Ghep te bao goc, Vien Huyet hoc - Truyen mau Trung i r ang t ir 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 d iem ghep.

Phiromg phap nghien cu>u: Nghien c i ru mo ta, khdng can thiep, theo ddi doc tien c i ru . Moi benh nhan d i rge theo ddi va ghi lai thong tin bat dau tir ngay ghep tdi thai diem benh nhan ngi rng sir dung thuoc khang nam, benh nhan chuyen sang phac dd dieu tri khang nam, benh nhan t ir vong hoac chuyen hoi s i re tfch cgc. Bp tieu chi danh gia d i rge nhdm nghien c i ru xay d g n g d g a tren h i rdng dan cua Mang l i rdi Ung thir Quoc gia Hoa Ky (National Comprehensive Cancer Network -NCCN) phien ban 2.2015 w va 2.2016 ®. Rieng cac tieu chf ve lieu dung cua voriconazol va f luconazol trong d g phdng khang nam d i rge tham khao tir t d thong tin san pham d i rge phe duyet tai Anh [ 6 ) do khdng d i rge de cap trong H i rdng dan cua NCCN. T i rang tac lien quan d i n thuoc khang nam d i rge xac djnh dga tren cudn Hansten and Horn's Drug Interaction Analysis and Management 2013 va Iga chpn cac t i rang tac t ir mire dp 3 t rd len m .

nam chf xet tren benh nhan cd chi dinh phu hgp va tieu chf ve thai gian d g phdng khang nam chi tfnh tren so benh nhan khdng tir vong, chuyen hoi s i re tfch c g c hoac n h i l m n l m trong qua trinh dieu trj.

Xir ly s o lieu: So lieu d i r ac x i r ly bang Microsoft Excel 2016 va SPSS 22.0.

Ket qua D a c diem c u a benh nhan H S C T trong m i u

nghien c i m Dac diem cua benh nhan HSCT trong m i u nghien

c i ru d i rge 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 19 -65 18-52 18-65 So benh nhan nam (%) 11/21(52,4%) 11/17(64,7%) 22/38(57,9%)

Trong mau nghien c i ru , so benh nhan ghep t g than nhieu han so benh nhan ghep dong loai. D p tuoi cua benh nhan trong m i u nghien c i ru phan bo rpng (18 -65), nhdm benh nhan ghep t g than cd dp tuoi cao h a n (19 - 65) nhdm benh nhan ghep dong loai (18 - 52). Benh nhan nam cd ty le cao han trong m l u nghien c i ru . 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 T A P C H I D U O C H O C - 1 1 / 2 0 1 7 ( S O 499 N A M 57)

• Nghien cCm - Ky thuat

100% of patients with median 17.5 days (13 - 47.5), 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.

Trong bo tieu chf, tieu chf chf dinh thuoc khang nam d i rge tfnh theo so benh nhan, con tieu chf Iga chpn thuoc, lieu dung, d i rdng di ing cua cac thuoc nay d i rge tfnh theo so

Oat v a n de

Ghep te bao goc tao mau (Hematopoiet ic stem cell transplantation - HSCT) la mot ky thuat phire tap, cd the gay ra nhieu bien ch i rng n g h i l m trong cho benh nhan, trong dd cd n h i l m n l m m . S i r dung thudc khang nam d g phdng tren doi t i r gng benh nhan ghep te bao goc dem lai nhieu Igi fch, tuy n h i l n , 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 t i rang tac cd lien quan d i n thuoc khang n a m l 2 ] . Khoa Ghep te bao goc, Vien Huyet hoc - Truyen mau Trung i r ang la c a s d dau nganh trong ITnh v g c ghep te bao goc tai Viet Nam. Day cung la nai cd ty I I n h i l m nam cao, chiem 40 ,9% so benh pham nam toan Vien, dong tha i , Khoa Vi sinh cua Vien cung da ghi nhan hien t i rgng g iam nhay cam cua Candida tropicalis vd i f luconazol P l . Tren c a s d dd , chung tdi tien hanh de tai nay vd i muc tieu phan tfch phac do d g phdng b l n g thuoc khang nam tren b i n h nhan g h l p te bao goc, t ir dd, de xuat d i rge cac bien phap gdp phan nang cao hieu qua sir dung thudc khang nam cua V i | n .

Doi tirgng va phircrng phap Doi t i rgng nghien cu>u: Toan bo b | n h nhan d i rge

t i l n hanh HSCT tai Khoa Ghep te bao goc, V i | n Huyet hoc - T r u y l n mau Trung i r ang t ir ngay 01/4/2016 den ngay 31/12/2016; loai trir b | n h nhan cd tuoi < 18 tuoi va b | n h nhan dang sir dung phac do d i l u trj khang nam tai thai diem ghep.

P h a a n g phap nghien c i n i : N g h i l n c i ru m l ta, khdng can thiep, theo ddi dgc tien c i ru . Moi b | nh nhan d i rge theo ddi va ghi lai thong tin bat dau tir ngay ghep tdi thai d i l m b | n h nhan ngi rng sir dung thuoc khang nam, b | nh nhan chuyen sang phac do d i l u trj khang nam, b | n h nhan tir vong hoac chuyen hoi s i re tfch cgc. Bp t i l u chf danh gia d i rge nhdm n g h i l n c i ru xay d g n g dga t r l n h i rdng dan cua Mang l i rd i Ung thir Quoc gia Hoa Ky (National Comprehensive Cancer Network -NCCN) phien ban 2.2015 M va 2.2016 w. Rieng cac tieu chf ve lieu dung cua voriconazol va f luconazol trong d g phdng khang nam d i rge tham khao t ir t d thong tin san pham d i rge phe d u y | t tai Anh [ 6 ) do khdng d i rge d l cap trong H i rdng dan cua NCCN. T i rang tac lien quan d i n thuoc khang n l m d i rge xac djnh dga tren cuon Hansten and Horn's Drug Interaction Analysis and Management 2013 va Iga chpn cac t i rang tac t ir m d e dp 3 t rd l l n m .

dg t d i l u trj (tire la khoang thai gian tfnh t ir luc bat dau den luc k i t thuc sir dung mot thuoc khang nam vd i muc dfch d g phdng). Ngoai ra, tieu chf Iga chpn thuoc khang nam chf x l t t r l n b | nh nhan cd chi djnh phu hgp va t i l u chf v l thai gian d g phdng khang nam chi tfnh t r l n so b |nh nhan khdng t ir vong, c h u y l n hoi sire tfch c g c hoac n h i l m n l m trong qua trinh dieu trj.

Xir ly s o lieu: So lieu d i r ac x i r ly bang Microsoft Excel 2016 va SPSS 22.0.

K e t q u a

D a c diem c u a benh nhan H S C T trong mau nghien cu>u

Dac diem cua b | n h nhan HSCT trong m i u n g h i l n c i ru d i rge 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 Ghep to than 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 19-65 18-52 18-65 So benh nhan nam (%) 11/21(52,4%) 11/17(64,7%) 22/38(57,9%)

Trong mau n g h i l n c i ru , so b | n h nhan ghep t g than nhieu han so b | n h nhan ghep dong loai. D p tuoi cua b | n h nhan trong mau nghien c i ru phan bo rpng (18 -65), nhdm b | n h nhan ghep t g than cd dp tuoi cao han (19 - 65) nhdm b | n h nhan ghep dong loai (18 - 52). B | n h nhan nam cd ty l | cao han trong mau n g h i l n c i ru . Da so cac b | n h nhan khdng ghi nhan tien s i r va b | n h m l c kem (81,6%). Tat ca b | n h 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 T A P C H I DUCfC H O C -11/2017 (SO 499 N A M 57)

• Nghien cfru - Ky thuat

40

30 .1

3 20 x

10

33

21

0 0 0

12

1 1

100% so benh nhan ghep deu d i rge d g phdng bang thuoc khang nam azol. Thudc d g g c sir dung nhieu n h l t la f luconazol (36 benh nhan, chiem 94,7%). Posaconazol va voriconazol chi d i rge sir dung d benh nhan ghep dong loai.

Ket qua phan tich phac do khang nam d g phong v a lieu dung t h g c te tren benh nhan s o vdi lieu khuyen c a o

Bang 3. Ket qua phan tich phac dd khang nam dir phdng Ghep tv than Ghep dong loai Toan bo mau

B Nhiem nam • Chuyen ICU

H Tu vong O Hoan thanh dieu tri

Hinh 2. Bien co sau ghep cua benh nhan trong nghien cuv Dac diem lien quan den ch i dinh thuoc khang

n l m d g phong

Bang 2. Dac diim lien quan den chi dinh thuoc khang nam dg phdng

Chi tieu nghien ciru Ghep to than Ghep dong loai Toan bp mau S6 benh nhan dir phdng nam(%) 21/21 (100,0%) 17/17(100,0%) 38/38 (100,0%)

Thdi gian diing (ngay-trung vivalQR)

16(13-17) 62(31 -73) 17,5 (13-47,5)

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%)

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 0/0 (Khong danh gia)

29/29(100,0%) 29/29(100,0%)

Lidu, dudng dung phu hop

0/22 (0,0%) 0/29 (0,0%) 0/51 (0,0%)

Thoi gian dung phii hop 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 ch i con lai deu co ty le phu hgp rat thap. Nhin chung, ty le phu h g p d nhdm benh nhan ghep t g than thap han nhdm benh nhan ghep dong loai. Dae biet, ve lieu dung va d i r dng dung, tat ca benh nhan deu d i rge sir dung thuoc khang nam phu h g p ve d i r dng dung nh i rng lieu dung thgc te cua cac thuoc nay deu thap han lieu d i rge khuyen cao. Cu the, lieu dung cua benh nhan d i rge tr inh bay trong bang 4.

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)

Lieu khuyen cao

Fluconazol

Cla > 50ml/phut 300 mg/ngay 19 16

400 mg/ngay Cla > 50ml/phut 150 mg/ngay 0 1

400 mg/ngay

CICr < 50 ml/phut

khdng toe mau

300 mg/ngay 0 1 200 mg/ngay

CICr < 50 ml/phut

khdng toe mau 150 mg/ngay 1 0 200 mg/ngay

Itraconazol 200 mg/ngay 2 2 400 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 0 5 200 mg x 3 lan/ngay

Dac diem tircrng tac thuoc co y nghTa lam s a n g 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 Ghep to than Ghep dong loai Toan bp mau 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 Azol1 - diazepam 20 (90,9%) 21 (72,4%) 41 (80,4%)

Azol1 - thuoc dc che mien dich2 0(0%) 25 (86,2%) 25 (49%)

Azol3 - 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 2Ciclosporin, tacrolimus ritraconazol, posaconazol

T i rang tac lien quan den thuoc khang nam d i r ge ghi nhan trong mau nghien c i ru vd i ty le rat cao, vd i 9 2 , 1 % benh nhan gap it nhat 1 t i r ang tac. T i r a n g tac pho bien nhdt la giCfa cac azol vd i d iazepam, gap d 80 ,4% so dgt d i i u tri cua benh nhan. T i r a n g tac giCra cac azol vd i cac thuoc ire che mien djch (ciclosporin va tacrol imus) cung d i rge phat hien trong 25 dg t dieu trj, ch iem 49 ,0%.

Ban luan Ket qua cua nghien c i ru cho thay, d g phong bang

thuoc khang nam d i rge chi dinh tren toan bp benh nhan tham gia nghien c i ru . Tuy nhien, chi co 17/38 chi djnh (chiem 44,7%) la phu hgp . Didu nay xuat phat t ir viec benh nhan ghep t g than khong cd bieu hien v iem niem mac van d i rge chi djnh thuoc khang nam khdng can thiet. T inh trang tren cung d i rge ghi nhan

(Xem tiep trang 46)

T A P C H I DlTCfC H O C - 11/2017 (SO 499 N A M 57) 4 1

• 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), 217-223.

7. Schneider L. S. (2000), "A critical review of cholinesterase inhibitors as a treatment modality in Alzheimer's disease", Dialogues Clin. Neurosci., 2(2), 111-128.

(Ngay nhan bai: 21/07/2017 - Ngay phan bien: 24/09/2017 - Ngay duyet dang: 20/10/2017)

Phan tich tinh hinh... (THp theo trang 41) trong nghien c d u cua Vazin va CS. theo doi trong s6 67 benh nhan s i r dung f luconazol, co 19,4% d i rge chi djnh khong phu hgp tren benh nhan ghep t g than khong co viem niem mac [ 8 ! . T inh trang nay co the xuat phat t ir khd khan trong viec quydt djnh chi djnh thuoc cho benh nhan ghep t g than khi ch i ra co cdng cu nao cho phep d g d o l n tr inh trang v iem niem mac va g iam bach c l u trung t inh.

Toan bd benh nhan trong m i u nghien c d u d i r ge d g phong bang cac thuoc khang nam nhdm azol. Trong do, f luconazol la thuoc d i rge s i r dung phd bien nhat. Tuy nhien, f luconazol cung d d n g dau trong cac thuoc d i rge chi djnh khong phu hgp , vd i ly do da d i rge de cap d phan chi djnh ch i ra hgp ly d tren. H a n naa , khong co benh nhan nao d i rge sir dung f luconazol vd i lieu phu hgp . Hien t i r gng t i rang t g da d i rge ghi nhan trong nghien cdu cua Nivoix va C S . M . D ieu nay cd the lien quan den viec d Vien chi co che pham f luconazol 150 mg vien nang va 200 mg truyen tTnh mach, trong do viec sir dung thuoc dung d i r dng udng d i rge sir dung pho bien va thuan tien han cho benh nhan. S i r dung f luconazol vd i lieu thap han binh th i rdng co the t iem I n nhieu nguy ca . Dac biet la khi Vien dang ghi nhan t inh trang gia tang de khang vd i f luconazol cua Candida tropicalis, ty le khang thuoc nam 2015 da len td i 4 4 % .

Trong nhdm benh nhan ghep t g than, tat ca benh nhan deu sir dung thuoc khang nam khi bach c l u da t rd ve mire binh th i rdng. Thong th i rdng, benh nhan chi d i rge ngdng thudc khang n l m khi t inh trang on djnh va x u l t vien. VI vay, viec keo dai thuoc khang nam gay lang phi chi phi dieu trj cho benh nhan. Ng i rgc lai, trong nhdm benh nhan ghep dong loai, da so benh nhan ngirng sir dung thudc tn rdc ngay t h d 75 sau ghep. Dieu nay la do thai gian nam vien cua da so benh nhan ghep dong loai v i rg t qua tran bao hiem, nen nhCrng benh nhan co tinh trang on djnh th i rdng d i rge x u l t vien t rade 75 ngay sau ghep. Khi dieu tri ngoai tru, cac benh nhan nay cung khdng sir dung thuoc khang n l m do gia thanh kha cao.

T a a n g t i e pho bien nhat ghi nhan trong m i u nghien c d u la t a a n g t i c g iaa c l c azol va d iazepam cd nguy c a Urn t i n g nong dp trong huyet t a a n g cua d iazepam, d i n den tang c l c bien cd bat Igi cua thudc n h a an t h i n q u i mdc , g i l m k h i nang phdi hgp c l c c d ddng, p h l n xa ( th l t d i eu ) [ 7 ] . Vd i benh nhan HSCT, d iazepam chi d a g c sir dung vd i muc dich an t h i n , vi vay, bac sT nen can nhac viec phdi hgp thudc n l y vd i c l c azol de han chd t i c dung bat Igi cho benh nhan. T a a n g t i c c l n chu y n h l t , dong thai I I t a a n g t i c d a g c c l n h b i o trong H a d n g d i n dieu trj cua NCCN I I t a a n g t i c gi ira c l c azol k h l n g nam v i c l c thuoc d c che mien djch (ciclosporin,

tacrol imus), cd the d i n den suy than trong t r adng h g p khdng d a g c kiem s o l t c h i t che M . Hien nay, Vien da cd nhdng bien p h l p g i l m s i t t ich c g c de g i l m thieu t a a n g t i c bat Igi n l y , bao gom g i l m s i t creatinin qua bd xet nghiem t h a d n g quy v i djnh l agng ndng dd thuoc trong m i u vd i tan s u i t 1 lan/tuan de kiem s o l t hieu q u i v i ddc t inh cua c l c thuoc dc che mien djch.

Ket luan Ket qua cua nghien c d u cho t h l y thgc trang s d dung

thudc k h l n g nam d g phdng tren benh nhan HSCT tai Vien Huyet hgc - Truyen m i u Trung a a n g . Nghien c d u da chi ra ty le khdng phu hgp cao trong s d dung thuoc k h l n g n l m d g phdng d doi t a g n g benh nhan n l y ve c l c tieu chi chi djnh, lieu dung v i thai gian dung. Dieu nay cho thay c l n thief then khai c h a a n g tr inh q u l n ly thuoc k h l n g n l m tai Vien nham nang cao c h i t l a g n g s d 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. 6274-6315.

2. Andes D., Azie N. et al. (2016), "Drug-drug interaction associated with mold-active triazoles among hospitalized patients", Antimicrob. Agents Chemother., 60(6), pp. 3398-3406.

3. 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 2.2015) , <https://www.nccn.org/professionals/physician_gls/ pdf/infections.pdf> [Accessed: 03/01/2016].

5. National Comprehensive Cancer Network (2016), Prevention and treatment of cancer-related infections (Version 2.2016) , <https://www.nccn.org/professionals/physician_gls/ 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), <http://www.medicines.org.uk/ 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. 97-102.

9. 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. 2506-2513.

(Ngay nhan bai: 19/09/2017- Ngay phan bien: 28/09/2017- Ngay duyet dang: 20/10/2017)

4 6 T A P C H I D U O C H O C - 11/2017 (SO 499 N A M 57)