TAP CHl Y DL/pC LAM S A N G 108 Tgp 6 - S6 3/2011
Danh gia hieu qua va an toan cua amikacin thong qua giam sat n6ng do thuoc trong mau benh nhan nhiem khuan ho hap tai Khoa Lao va Benh phoi, Benh vien Trung uo-ng Quan doi 108
Evaluation the efficacy and safety of amikacin by measurement of drug concentration in the blood of patients with respiratory tract infection at the Department of Tuberculosis and Lung diseases in the 108 Military Central Hospital
Pham Thj Thuy Van' 'Truang Dai hoc Duac Hd Noi Nguyen San Nam^, Dinh Dinh Chinh^ ^Benh vien Trung uong Qudn doi 108
Tom tat
Amikacin la khang sinh co pham vi dieu tri hep, hieu q u i diet khuan phu thuoc vao nong dp, can dupc giam sat nong dp thuoc/huyet thanh trong qua trinh dieu tri. Mue tieu: danh gia hieu qua va an toan cua amikacin dieu trj cho benh nhan nhiem khuan h6 hap tai Khoa Lao va Benh phoi - Benh vien T U Q O 108.
Phuong phap: lay cac mau mau eua benh nhan de djnh lupng nong dp dinh (CpeaO va nong dp day (Ctmugh) eCia amikacin trong huyet thanh. Ket qua: danh gia hieu qua dieu trj dUa vao chi so Cpeak co 60% benh nhan dat nong dp yeu cau, ve tinh an toan cua viec sd dung amikacin: 70% benh nhan dat nong dp day theo khuyen cao. 100% benh nhan dung lieu 500mg x 1 lan/ngay deu kh6ng dat nong dp dinh va nong dp day. Ket luan: nong dp thuoc trong mau benh nhan chju tac dpng eua nhieu yeu to do vay de nang cao hieu q u i dieu trj va dam bao tinh an toan khi sddung amikacin can giam sat nong dp thuoc trong qua trinh dieu tri.
TCf khoa: Amikacin, nong dp thuoc, Cpeak, Ctrough.
Summary
Amikacin is an antibiotic with a narrow therapeutic range and concentration - dependent bactericidal effect, should be monitored drug serum concentration during treatment. Aims: to evaluate the efficacy and the safety of amikacin in treatment of respiratory infection patients in the Department of Tuberculosis and Lung Diseases - 108 Central Military Hospital. Methods: peak concentration (Cp^k) and bottom concentration (Ctrough) of amikacin in serum at steady state were measured by Roche/Hitachi cobas C6000 at the Bach Mai Hospital.. Results: the rates of patients had achieved Cpeak, and Ctrough in the recommended ranges were 60%
and 70,0%. 100% of patients using the dose of 500mg once daily did not reach the recommended peak and trough concentrations. Conclusions: drug concentrations in blood of patients affected by so many factors, thus, to enhance the efficacy and the safety of amikacin it should be monitored medication levels during the course of treatment.
Keywords: Amikacin, drug concentration, Cpeak, Ctrough
Plian bifn khoa hgc: PGS.TS. HOANG THI KIM HUYEN
JOUf^NAL OF 108 - CLINICAL MEDICINE AND PHARMACY Vol 6 N°3/2011 1. Oat van de
Trpng vdng 25 nam trd lai day, giam s i t thuoc trong dieu trj (Therapeutic Drug Monitoring -TDM) vdi nhdm khang sinh aminoglyeosid thdng qua nong dp thuoc trong huyet thanh d i ddpc thdc hien d nhieu nddc tren the gidi va dan trd thanh xet nghiem thddng quy. Tuy nhien tai Viet Nam, TDM van chda ddpc trien khai thdc hien ma
mdi ddpc k h i o sat t h d nghiem d mot so de tai nghien cdu.
Amikacin la khang sinh nhdm aminoglyeosid, ddpc sd dung de dieu trj cac nhiem khuan benh vien do vi khuan Gram i m hieu khi, die biet la cic nhiem khuan da khang eae aminoglyeosid khac. Tuy nhien, amikacin cung nhd cic aminoglyeosid la khing sinh ed khoang dieu trj hep, d i e diem diet khuan phu thuoc nong dp, dpc tinh cao tren than va tien dinh 6e tai. Oe toi du hoa hieu qua va ban che t i e dung kh6ng mong muon, cic y van deu yeu cau ke lieu tinh theo trpng Idpng benh nhin, hieu chinh lieu vdi benh nhan suy than va can p h i i giam s i t nong dp thuoc trong dieu trj.
Td cic die diem tren chung toi tien hanh nghien edu de t i i nay n h i m cic muc tieu:
/. Ddnh gid hieu qud viec sd dung amikacin tren ca sd so sdnh Cpeak vdi cdc hudng dan dieu trj.
2. Ddnh gid tfnh an todn viec sd dung amikacin tren ca sd so sdnh Chough vd nong do creatinin huyet thanh vdi cdc hUdng dan dieu tri.
Td ket q u i thu ddpc de xuat cic bien p h i p nham giup viec sd dung amikacin hieu q u i va an toan hon. •
2. Doi tupng va phUorng phap nghien cUu 2.1. Doi tUcfng nghien cdu
30 benh nhan dieu trj nhiem khuan ho hap tai khoa Lao va Benh phoi, Benh vien TLfQD 108 t d t h i n g 2 den t h i n g 7/2010.
* 77eu chuan lUa chon:
- Benh n h i n ngddi Idn (> 16 tuoi).
- Benh nhan ddpc xet nghiem nong dp creatinin trong mau trddc khi dung amikacin va it nhat 1 lan sau 3 - 5 ngay sau do.
- Ddpc lay m i u va djnh Idpng nong dp amikacin theo dung protocol nghien edu.
* Tieu chuan loai trd:
- Benh nhan lao.
- Benh nhan cd thdi gian dung khang sinh <3 ngay.
- Benh n h i n ed cac yeu to lam thay doi the tich p h i n bo cua thuoc nhd beo phi, mat djch ngoai b i o ning, benh nhan ed co trddng hoac phu nang...
Benh nhan kh6ng ddpc lam xet nghiem chdc ning than trddc khi sd dung amikacin.
2.2. PhUcfng phip nghien cdu M6 t i tien edu khong can thiep.
+ Chpn mau: chung toi Ida chpn benh nhan v i o mau nghien cdu theo cic tieu chuan d mue 2.1 va thu thap th6ng tin benh nhan theo'phieu.
+ Quy trinh nghien cdu:
Lda chpn benh nhan phu hpp vdi tieu chuan vao mau nghien edu, lieu dung amikacin va cac thuoc khic do b i c sT ehi djnh.
Lay mau de djnh Idpng nong dp amikacin td lieu thd 3 trd di, mau 1 (do Crough) lay ngay trddc khi tiem b i p ; mau 2 (do Cpeak) lay sau 60 phut ke t d khi tiem. Cic mau m i u ddpc xd ly va b i o q u i n trong tu lanh -40°C tai trddng Oai hpc Ddpc Ha Npi. Q u i trinh djnh Idpng nong dp thuoc thdc hien tai khoa Sinh hoa - Benh vien Bach Mai bang may do Roche/Hitachi cobas C6000 sd dung vdi modul C501, kit djnh Idpng: No.03376265 eua hang Roehe- Thuy Sy.
-I- Cac chi tieu danh gia:
O i n h gia ve lieu dung: sd dung mdc lieu khuyen c i o cua amikacin la t d 15-20mg/kg can nang tren BN ed chdc nang than binh thddng va phdpng p h i p hieu chinh lieu theo chdc nang than theo tai lieu AHFS Drug information 2009 de d i n h g i i lieu dung tren benh nhan.
TAP CHl Y DLTOC LAM SANG 108 Tap 6 - So 3/2011
- Danh gia hieu q u i dieu trj: Dda vao nong dp Cpeak do duac [3], [4]
Che dp lieu 1 lan/ngay Cpeak < 45 hoac > 64 pg/ml: Khong dat 45 < Cpeak s 64 pg/ml: Oat
Che dp lieu 2 lan/ngay Cpeak < 15 hoac > 30 pg/ml: Kh6ng dat 15 s Cpeak < 30 pg/ml: Oat
• Oanh g i i dp an toan: Dda vao chi so Cough [3], [5]
Che dp lieu 1 lan/ngay Ctrough ^ 1 ng/ml: An toan
Ctrough > 1 pg/ml: Khong an toan
Che dp lieu 2 lan/ngay Ctrough ^ 10 pg/ml: An toan
Ctrough > 10 pg/ml: Khong an toan 2.3. Phuang phip xdlysd lieu
Ket q u i nghien edu ddpc xd ly bang phan mem SPSS 13.0. Sd dung test T de so sinh hai g i i trj trung binh, test x^de so sinh hai ty le. Sd khic biet ed y nghla thong ke khi p < 0,05.
3. Ket qua nghien cUu
3.1. Die diem chung cua benh nhan nghien cdu
Tong so benh n h i n ddpc thu n h i n v i o nghien edu la 30, trong do cd 9 BN dung lieu 500 mg x 1 lan/ngiy (nhdm 1) va 21 BN dung lieu 500 mg x 2 lan/ngiy (nhdm 2). Mot so d i e diem chung v i die diem ve benh ly eua benh n h i n ddpc trinh b i y trong b i n g 3.1.
BSng 3.1. D i e diem eua benh n h i n nghien edu
Chi tieu
Gidi tinh
Chdc nang than
Benh ly ho hap
Nam Nd
Tong Giam chdc nang than nhe (50<Cler < 80 ml/ phut) Giim chdc nang than TB (10<Clcr<50ml/phut)
Tong Viem phoi
COPD boi nhiem Benh NKHH khac
Tong
Nhom 1 So BN (%)
5 (55,6) 4(44,4) 9(100) 2 (22,2)
7 (77,8) 9(100) 1(11,1) 3 (33,3) 5 (55,6) 9(100)
Nhom 2 So BN (%)
17(81,0) 4(19,0) 21(100) 8(38,1)
13(61,9) 21(100)
7(33,3) 9(42,9) 5(23,8) 21(100)
Chung So BN (%)
22 (73,3) 8 (26,7) 30(100,0)
10(33,3)
20 (66,7) 30(100,0)
8 (26,7) 12(40,0) 10(33,3)
30
P
>0,05
JOURNAL OF 108 - CLINICAL MEDICINE AND PHARMACY Vol 6 - N 3/2011
Chi tieu
Tuoi TB (nam) Can nang TB (kg)
Thdi gian nam vien TB (ngay) Thdi gian diJng KS TB (ngay) Thdi gian dung amikacin TB (ngay)
Nhom 1 So BN (%)
70,4±9,4 39,9±5,9 11,0±5,0 10,8±5,1 9,7±3,7
Nhom 2 So BN (%)
70,7±9,4 45,6±4,7 13,1 ±5,5 12,0±5,1 11,1 ±4,4
Chung So BN (%) 70,6 ± 9,2 43,9 ± 5,6 12,5 ±5,4 11,6 ±5,1 10,6 ±4,2
P
<0,05
Ghi chu: Cler (clearance creatinin): dp thanh thai creatinin, BN: benh nhan.
COPD (Chronic Obstructive Pulmonary Disease): Benh phoi tac nghen man tinh.
- Cac benh n h i n nghien cdu ed dp tuoi trung binh la 70,6 tuoi, tat ca BN cd g i i m chdc nang than vdi Cler < 80 ml/phut. D i y la ngddng ma trong nhieu tai lieu khuyen cao can hieu chinh lieu va giam sat nong dp thuoc trong m i u [3], [4] va la nhdm benh nhan ed nguy eo cao x i y ra dpc tinh khi sd dung khing sinh nhdm aminoglyeosid.
Trong mau nghien edu, doi tdpng benh nhin dieu trj dpt COPD cap boi nhiem chiem ty le cao nhat:
40%; sau do la BN viem phoi chiem 26,7%.
Thdi gian nam vien cua benh nhin k h i dai (trung binh khoang 2 tuan) trong do thdi gian sd dung amikacin la khoing 10 ngay.
3.2. Die diem velieu dung cua benh nhan nghien cdu
BSng 3.2. Die diem ve lieu dung eCia benh nhan nghien edu
Chi tieu
Oanh gia ,ve
lieu dung
Lieu thap hPn khuyen cao Oung lieu khuyen cao Lieu cao hon khuyen cao
Tong Lieu dung TB (mg/kg/ngay) Lieu dung TB (mg/kg/lan)
Nhom 1 So BN (%)
2 (22,2) 7(77,8)
0 9(100,0) 12,8±1,6 12,8±1,6
Nhom 2 So BN (%)
0 0 21 (100,0) 21(100,0)
22,0±2,5
n,o±i,2
Chung So BN (%)
2 (6,7) 7 (23,3) 21(70,0) 30(100,0)
19,2 ±4,8 11,5±1,6
P
<0,05
>0,05 Tat c i benh n h i n trong mau nghien edu deu ddpc dung amikacin theo dddng tiem b i p . 6 nhdm 1 (dung lieu 1 lan/ngay) cd 7/9 BN dung dung lieu khuyen cio, 2 BN dung lieu thap hon khuyen cao. Ngdpc lai, 100% BN d nhdm 2 (dijng lieu 2 lan/ngay) dijng cao hon lieu khuyen cio.
3.3. Dinh gii hieu qui cua viec sddung amikacin dUa vio chi so Cpeak Phin bo benh n h i n theo nong dp dinh ddpc trinh bay trong hinh 3.1 va b i n g 3.3.
TAP CHi Y D a p c LAM SANG 108 Tap 6 - 5 6 3/2011
Biiig 3.3. Phin bd benh nhin theo khoing nong dp dinh cua amikacin
An toan
Khong dat Oat Tong so
Che dp lieu 1 lan/ngay S6BN
9 0 9
Ty le (%) 100,0 .0,0 100,0
Che dp lieu 2 lan/ngay SoBN
3 18 21
Ty le (%) 14,3 85,7 100,0
Chung SoBN
12 18 30
Ty le (%) 40,0 60,0 100
Phan bo nong do dinh 35
• 30 C- 25
E
"3) S 20
I ''
c 10
; • >
•
•
10 20
• 1 lan/ngdy A 2 lan/ngay
30 40 S6 thirty
Hinh 3.1. Phdn bdnong do dinh cua cdc BN trong mdu nghien cdu
Phan bo nong do day
6
= • 5 - 1
«« 3
•O (O-
<0 2 o>
c
Z 1
• • • • .
• •
10 20
• 1 ian/ngdy ) 2 l^n/ngdy
30 40 So thiF t v
Hinh 3.2. Phdn bd nong do ddy cua cdc BN trong mau nghien cdu
-Ooi vdi cic BN dung*ehe dp lieu 500mg, 1 lan/ngiy, nong dp dinh (Cpeak) eua amikacin trong m i u nim trong khoing t d 16,0 - 32,1 pg/ml, dat g i i trj trung binh la 24,4 ± 5,0 ng/ml. Vdi khoing nong dp niy, khong CO benh nhin nao dat Cpeak theo yeu cau.
- Ooi vdi cic BN dung che dp lieu 500mg, 2 lan ngay, nong dp dinh (Cpeak) cua amikacin nim trong khoing t d 18,5-30,8 ng/ml, dat g i i trj trung binh la 25,4 ±3,3 ng/ml. Vdi khoing nong dp nay, hau het cic b^nh nhan (85,7%) dat Cpeak theo yeu cau, ehi ed 3 BN (14,3%) la nong dp cao, vdpt ngoii khoing khuyen cio nhdng cic nong dp nay cung cao hon rat it so vdi ngddng khuyen cio.
3.4. Dinh gii tinh an toan cua viec sddung amikacin
Phin bo benh nhan theo nong dp d i y ddpc trinh bay trong hinh 3.2 va ket q u i dinh g i i nong dp d i y ddpc trinh bay d b i n g 3.4.
JOURNAL OF 108 - CLINICAL MEDICINE AND PHARMACY Vol 6 N°3/2011
Bang 3.4. Phin bo benh nhin theo khoang nong dp day eua amikacin
An toan
Khdng dat Oat Tong so
Che dp lieu 1 lan/ngay SoBN
9 0 9
Ty le (%) 100,0
0,0 100,0
Che dp lieu 2 lan/ngay SoBN
0 21 21
Ty le (%) 0,0 100,0 100,0
Chung SoBN
9 21 30
T^le(%) 30,0 70,0 100,0
- d nhdm BN dung lieu 1 lan/ngay, nong dp d i y cua amikacin trong m i u nam trong khoing 1,4-2,1 jjg/ml, trung binh la 1,7 ng/ml. Vdi ngddng nong dp toi Uu la <1 jjg/ml, khong benh nhin nao dat mdc nong dp toi du.
6 nhdm BN dung lieu 500mg x 2 lan/ngiy, nong dp d i y eua amikacin trong mau nam trong khoing l,3-5,5|jg/ml, trung binh la 2,4 ng/ml. Vdi ngddng d i n h g i i la <10 pg/ml, tat ea cic BN deu dat toi Uu ve nong dp diy.
4. Ban luan
4.1. Ve die diem benh nhan nghien cdu Hai nhdm benh n h i n ed d i e diem tdong dong ve tuoi trung binh, thdi gian nam vien, thdi gian dung khang sinh, thdi gian sddung amikacin, mdc dp suy g i i m chdc n i n g than va lieu dung cho 1 lan tiem (p>0,05) nhdng khdng tdong dong ve mot so d i e diem khic nhu gidi tinh, can nang trung binh. 6 nhdm 1, ed nhieu benh nhan nd hon, can n i n g trung binh thap hon. Nhd v i y b i c sy d i chpn mdc lieu thap hon cho cic benh nhan niy.
Ve lieu dung: theo hddng dan cua nha sin xui't va eua DTQG VN, lieu dung eua amikacin la 15mg/kg/ngay cho BN cd chdc n i n g than binh thddng, nhdng mot so tai lieu nhd Hddng dan dieu trj eua Bp Y te n i m 2006, ed hddng dan mdc lieu 20mg/kg/ngay cho BN nhiem khuan n i n g . Do v i y , chung toi sddung mdc lieu 15-20mg/kg/ngay la khoing lieu chuan cho BN cd chdc n i n g than binh thddng va sd dung phdong phap giam lieu CO sda doi t d phdong phap cCia Sarubbi va
Hull ddpc sd dung trong tai lieu AHFS Drug Information de danh g i i lieu tren BN suy than [6].
Theo phdong p h i p d i n h g i i nay, ehi ed nhdm 1 la cd nhieu BN cd mdc lieu sd dung nam trong khoing lieu khuyen c i o (7/9BN). Do sd dung lieu lam trdn theo don vj ddng gdi I i Ip 500mg nen lieu dijng d nhdm 2 rat cao, tham ehi ed nhdng BN ddpc sd dung mdc lieu cao gap doi lieu toi da khuyen c i o . Neu cic BN nhdm 2 ehi dung lieu 1 Ip/ngay nhd vdi nhdm 1 thi ed den 17/21 (81,0%) BN se dat va chi ed 4 BN la ed lieu thap hon khuyen c i o . Hon nda, each dung lam trdn lieu nay lam cho lieu dung dao dpng Idn gida 2 nhdm, mdc lieu trung binh d nhdm 2 cao gap 1,7 lan d nhdm 1 trong khi c i n n i n g trung binh ehi cao hon 1,14 lan.
4.2. Hieu qui cua viec sd dung amikacin dUa
vio chi so Cpeak
Oe d i n h g i i hieu qua sd dung eua amikacin dCing 1 lan/ngay, chung toi chpn ngddng nong dp dinh la 45 64 jig/ml la toi du theo hddng dan sd dung khang sinh eua Sanford va mot so tai lieu khac [4]. Dda theo chi tieu d i n h gia nay thi tuy ty le Idn benh nhan ddpc sd dung dung lieu khuyen cao, nhdng 100% benh nhan khdng dat nong dp dinh toi du vdi g i i trj trung binh la 24,4 ± 5,0 pg/ml. Ty le nay tdong ddOng vdi mot nghien cdu e6ng bo nam 2007, tren eae BN dung che dp lieu tdOng t d [2]. Cic so lieu trong eae nghien edu nddc ngoai cho cac gia trj dao dpng rat Idn ve nong dp dinh. Mot nghien edu djnh Idpng nong dp dinh eua amikacin tren 191 benh n h i n dung lieu 20mg/kg/x 1 lan/ngay cho thay nong dp dinh trung binh eua nhom BN nay la 126
TAP CHi Y DLfOC LAM SANG 108 Tap 6-56 3/2011 48,3+ 20,2 pg/ml [7]. So vdi cac nghien edu tren,
mdc lieu dung trong nghien edu eua chung tdi thap hon, nen g i i trj nong dp dinh cung dat duac rat thap. Tuy nhien, khi so sinh vdi mot nghien cdu khic tien hanh tren 101 BN dung lieu tieu chuan 15mg/kg cua amikacin cho BN ed chdc ning than binh thddng va ed hieu chinh theo chdc ning t h i n (mdc lieu dung tuong t d nhd trong nghien cdu cua chung tdi) cho thay nong dp dinh trung binh la 40,9 pg/ml, cao hon nhieu so vdi nhdm BN cCia chung tdi [5].
Trong nhdm BN dung 2 lan ngiy, mac du 100% benh n h i n dung lieu cao hon khuyen cio, ty le BN dat nong dp dinh cao hon nhieu so vdi nhdm 1 (85,7%), chi cd 14,3% benh nhan ed nong dp vdpt khoing khuyen cao, nhung mdc chenh lech rat thap (0,8pg/ml). Nong dp dinh trung binh eua nhdm benh n h i n nay la 25,4 ± 3,3 pg/ml. Cic so lieu d i cdng bo ve nong dp dinh khic biet k h i Idn gida cic nghien cdu. Trong mot nghien edu tren 929 benh n h i n diJng amikacin vdi lieu 300-500mg x 2 lan/ngay, ty le benh n h i n ed Cpeak
<25 pg/ml I i 53,3%, t d 25-35 pg/ml I i 31,6%,
>35pg/ml I i 15,1%, trong khi d nghien cdu eua chung tdi, vdi mdc lieu dong loat 500mg, 2 lan/ngay, cic ty le BN tdong dng I i 38,8%, 61,2%
va 0% [3].
- Nong dp dinh trung binh d 2 che dp lieu trong mau nghien cdu khic nhau khdng ed y nghla thong ke. Ly do I i gida 2 nhdm, tuy lieu dung/ngay khic biet rat Idn, nhdng lieu dung/Ian lai tdong ddong nhau, dan den khdng cd sd khic biet ve nong dp dinh sau 1 lan tiem.
- Chung tdi d i n h g i i moi lien quan gida nong dp dinh va mot so yeu to anh hddng nhd lieu dung cija llan tiem, chdc ning than, nhdng khdng tim ddpc moi tdong quan chit che gida eae yeu td nay vdi nong dp dinh. Nhd vay ed the noi, nong dp dinh dao dpng Idn, khong ed moi tdong quan chit vdi lieu dung va thap hon so vdi nong dp ddc tinh la die diem noi bat d nhdm benh n h i n nghien cdu v i do vay viec djnh Idpng nong dp thuoc trong m i u can ddpc xem xet ap dung thddng quy nhim ning cao hieu q u i dieu trj.
4.3. Dp an toan cua viec sddung amikacin
Trong nghien edu nay, cd tdi 100% benh n h i n dijng lieu 1 lan/ngay khong dat nong dp d i y theo khuyen c i o . So vdi nghien cdu trudc dd cdng bo n i m 2007 cd che dp lieu trUOng tu, ty le benh n h i n khong dat nong dp d i y trong nhdm dung 1 lan/ngiy ehi I i 23,3%[2] ed the I i do nhdm BN cua chung tdi cd nhieu benh n h i n g i i m chdc n i n g than hon. Trong nhdm 1, ed 7/9 BN (77,8%) cd dp thanh t h i i creatinin kha thap (30-<40ml/phut), trong khi d nghien cdu tren, eon so n i y I i 10%.
Ooi vdi cic benh n h i n ed dp thanh t h i i thap nhu v i y , ti/2 Lfde d o i n eua amikacin vao khoing 8,5h, va trong mot so tai lieu, khuyen c i o can g i i m s i t nong dp d i y de g i i n khoing dUa lieu cho nhdm benh n h i n n i y va khoing dda lieu ed the dai hon 24h (vi du 36-48h). Trong nghien edu thd hai ddpc tien hanh d i ed can thiep ve lieu dung v i khoing du'a lieu dUa vao cic thdng so ddpc dpng hpc d i e trdng eua nhdm benh n h i n , ty le benh nhan khdng dat nong dp dinh v i d i y g i i m xuong (tuong dng la 32% v i 16%)[1]. Dieu n i y cho thay viec xac djnh cic thong so dupe dpng hpc tren tdng quan the benh n h i n , ddng thdi g i i m s i t dieu trj dda v i o cic thdng so n i y I i phdOng p h i p hdu ich nhat l i m gia t i n g k h i n i n g dat cic nong dp hieu q u i va an toan cua thuoc.
Trong nhdm benh n h i n dung lieu 2 lan/ngiy, cic so lieu ve nong dp d i y eua nghien edu chung toi v i mot so t i i lieu nude ngoii dao dpng k h i Idn. Mot khio s i t nong dp d i y eua 929 benh n h i n dung amikacin vdi lieu 300-500mg x 2 lan/ngiy, ty le benh n h i n ed Ctrough <1 pg/ml I i 20%, t d 1-10 pg/ml la 71,2 %, >10pg/ml la 8,8%
[3], trong khi d nghien cdu eiJa chung toi, vdi mdc lieu dong loat 500mg, 2 lan/ngay, 100% BN ed nong dp day t d 1 -10 pg/ml. Trong mot nghien edu khic, nong dp d i y cua 234 BN dCing che dp lieu tdong tp nhu trong nghien cdu chung tdi (20mg/kg chia nhieu lan/ngay) I i 4,0±6,1pg/ml[7].
Mot diem can Idu y I i trong nghien edu eua chung tdi, thuoc ddpc tiem lam 2 lan khoing luc 8 -9h sing va 14-15h chieu dan den khoing dda lieu
JOURNAL OF 108 - CLINICAL MEDICINE AND PHARMACY Vol 6 N°3/2011 k h d n g d o n g d e u . Tat c i c i c mau Crough d e u d d p c
lay vao b u o i s i n g , nen n o n g d p d i y k h i t h a p c i c h t h d i d i e m d u n g t h u o c t r d d c d o la 18 g i d c h d k h d n g p h i i 12 g i d n h d k h u y e n c i o , nen n o n g d p d i y t h u d d p c kha t h a p (2,4 p g / m l ) .
Trong mau nghien edu, chung t6i kh6ng t i m thay m o i lien quan gida n o n g dp day va m o t so yeu t o n h d mdc dp suy g i i m chdc n i n g than, t u o i eua benh nhan va sp khac biet gida lieu sd d u n g khi phan tich anh h d d n g d o n bien. N h d v i y , c i c yeu t o i n h h d d n g den n o n g d p d i y eua t h u o c dan xen rat phdc tap, va do v i y , can k h i o s i t t h e m c i c t h 6 n g so d d p c d p n g hpc tren n h d m benh nhan nay de g i u p thiet ke che d p giam s i t dieu trj thuoc, nham n i n g cao hieu q u i v i an toan dieu trj.
5. Ket l u a n
Ve t i n h hieu q u i eua viec sd d u n g amikacin:
t r o n q 30 BN duac danh gia hieu q u i dda tren n o n g d p d i n h (Cpeak) cua amikacin ed 6 0 % BN dat nong d p hieu q u i .
Ve t i n h an t o i n eua viec sd d u n g amikacin:
70% BN dat nong d p d i y theo khuyen c i o .
100% BN diJng lieu 500mg x 1 lan/ngay deu khdng dat c i n o n g dp dinh v i nong dp day.
Dexuat
Can cd eae nghien edu k h i o s i t c i c t h d n g so ddpc d p n g hpc tren quan the benh nhan dieu trj tai khoa Lao va Benh phoi vdi c d mau Idn de t d do tinh t o i n lieu diJng ban dau hpp ly va x i y d d n g quy trinh giam s i t dieu trj nhiem khuan bang amikacin.
- Can duy tri ke lieu theo trpng Idpng benh nhan, tuyet doi khdng ke theo don vj d d n g gdi eua thudc.
Tai l i e u t h a m ichao
1. Nguyen Hong Thuy, Duong Thanh Hai, Nguyen Thi Hong Gam va cs (2009), "Oanh gia viec sd dung mot so khang sinh tai khoa dieu tri tich cUc, benh vien Bach Mai thong qua theo doi nong dp thuoc trong mau", Bao cao Hoi thao toan quoc ve Cap edu- Hdi sdc- Chong doe lan t h d 9.
2. Pham Thi Thuy Van, Nguyen Lien Huong, Hoang Kim Huyen, Nguyen Thu Van (2007), Evaluation amikacin use by monitoring plasma drug concentration in patients at intensive care unit - Bach mai hospital, Pharmaco Indochina IV, November 21-24, PC-0-1.
3. Adjepon-Yamoah ( 2000), "Aminoglyeosid usage and monitoring ina Saudi Arabian teaching hospital: a ten-year laboratory audit". Journal of clinical pharmacy and therapeutics 25:303-307.
4. Laurence L B, John S. L, Keith L P(2006), Goodman &
Gildman's The pharmacological basic of therapeuties- 11*Ed., McGraw-Hill, Chapter 45.
5. Mailer R (1993), "Once- versus twice - daily amikacin regimen: efficacy and safety in systemic Gram - negative infections". Journal of antimicrobial chemotherapy 31,939-948.
6. McEvoy G.K (Editor), AHFS Drug Information (2009), Am Soc of Health System.
7. The International Antimicrobial Therapy cooperative Group of the European Organization for research and Treatment Cancer (1993), "Efficacy and Toxicity of single daily doses of amikacin and ceftriaxone versus multiple daily doses of amikacin and ceftazidime for infection in patients with cancer and granulocytopenia", Ann Intern Med 119:584-593.
