Qui trình theo dõi trị liệu áp dụng cho Vancomycin 5 III.. Qui trình theo dõi trị liệu áp dụng cho Digoxin 10... Cmax Nồng độ tối đa Cmin Nồng độ tối thiểu TDM : Therapeutic Drug Monitor
Trang 1SỞ KHOA HỌC VÀ CÔNG NGHỆ TP HỒ CHÍ MINH
(Các sản phẩm nghiên cứu theo HĐ số 294/HĐ-SKHCN ký ngày 27 tháng 12 năm 2006)
Cơ quan quản lý: Sở khoa học và công nghệ TPHCM
Cơ quan chủ trì: Trung tâm khoa học công nghệ Dược Sài gòn
Đại học Y Dược Chủ nhiệm đề tài: PGS TS Mai Phương Mai & TS Phan Thị Danh
TP Hồ Chí Minh, 07/2009
Trang 2TẬP QUY TRÌNH
(Các sản phẩm nghiên cứu theo HĐ số 294/HĐ-SKHCN ký ngày 27 tháng 12 năm 2006)
Cơ quan quản lý: Sở khoa học và công nghệ TPHCM
Cơ quan chủ trì: Trung tâm khoa học công nghệ Dược Sài gòn
ĐỀ TÀI:
“XÂY DỰNG QUI TRÌNH THEO DÕI TRỊ LIỆU DỰA TRÊN NỒNG ĐỘ CỦA MỘT SỐ THUỐC
CÓ GIỚI HẠN TRỊ LIỆU HẸP Ở NGƯỜI VIỆT NAM”
Chủ nhiệm đề tài: PGS TS Mai Phương Mai & TS Phan Thị Danh
Cơ quan phối hợp chính: BV Chợ Rẫy, BV Trưng Vương
BV Nhân dân Gia Định
Cộng tác viên phối hợp chính:
PGS.TS Bùi Tùng Hiệp BV Trưng Vương
ThS Nguyễn Thanh Nhàn BV Nhân Dân Gia Định
TS Nguyễn Tuấn Dũng ĐH Y Dược, Khoa Dược
TS Võ Phùng Nguyên ĐH Y Dược Khoa Dược ThS Đặng Nguyễn Đoan Trang ĐH Y Dược-BV Nhi Đồng 1 ThS Nguyễn Hương Thảo ĐH Y Dược-BV Chợ Rẫy ThS Trần Thủy Tiên ĐH Y Dược, Khoa Dược
Thời gian thực hiện: Từ tháng 12/2006 - 03/200
Trang 3MỤC LỤC
Trang
I Qui trình theo dõi trị liệu áp dụng cho Aminoglycosid 1
II Qui trình theo dõi trị liệu áp dụng cho Vancomycin 5
III Qui trình theo dõi trị liệu áp dụng cho Theophylin 8
IV Qui trình theo dõi trị liệu áp dụng cho Digoxin 10
Trang 4Cmax Nồng độ tối đa
Cmin Nồng độ tối thiểu
TDM : Therapeutic Drug Monitoring Theo dõi trị liệu
(bằng giám kiểm nồng độ thuốc) Time Css Thời gian đạt nồng độ ổn định
Trang 5TÀI LIỆU THAM KHẢO
1 Abbott Laboratorries Diagnostics Division (2006), Abbott AxSYM® Digoxin II
2 American Society of Health – System Pharmacists (2007), AHFS Drug
Information, USA, pp 3487 – 3493
3 Burtis C A., Ashwood E R (1999), Tietz Textbook of Clinical Chemistry W.B
Saunders Company, London, 94 – 97, 886 – 888
4 Dasgupta A (2008), Handbook of drug monitoring method, Humana Press pp
1-39, 78-79
5 Destache CJ, Meyer SK, Bittner MJ, Hermann KG (1990), “Impact of clinical pharmacokinetics services on patients treated with aminoglycosides: A cost-benefit
analysis”, Ther Drug Monit., 12: 419-426
6 Evans W E, Schentag J J, Juoko W J (1986), Applied pharmacokinetics:
Principles of Therapeutic Drug Monitoring, 2nd, Applied thepeutics Inc, USA, pp
1105 -1172
7 Gutshall E.D., Davidson H.E., Davis S.K (1999), Theophylline, Medication usage
evaluation : a screening criteria manual, Insight therapeutics, LLC
8 Hermsen E D (2008), Pharmacokinetic Training Packet for Pharmacist,
Nebraska Medical Center: Clackson and University Hospital
9 Herry J B (2002), Clinical Diagnosis & Management by Laboratory Methods,
W.B Sauders Company
10 Koda-Kimble M.A Young L.Y., (2000), Applied therapeutics: the clinical use of
drugs, 7th, Applied therapeutics, Inc USA
11 Moffat A Therapeutic Drug Monitoring(2004), Clarke’s Analysis of Drug and
Poisons Pharmaceutical Press, London, 148 – 153
12 Micromedex Thomson Healthcare (2002), Drug Information for the Health Care
Professional, 22nd, The US Pharmacopeial Convention Inc, pp 689 – 703
13 Pervaiz M H , Michael G Dickinson, Mohammad Yamani (2006), “Is Digoxin
The Drug Of The Past”, Cleveland Clinic Journal Of Medicine, 73, 821-834
14 Ried LD, Mc Kenna DA, Horn JR (1989), “Meta-analysis of research on the effect
of clinical pharmacokinetics services on therapeutic drug monitoring”, Am J Hosp
Pharm, 46: 945-951
Trang 615 Schumacher G E (1995), Therapeutic Drug Monitoring, Appleton & Lange, ConnecticutTerence J Campell & Peter S MacDonald (2003), “Digoxin In Heart
Failure And Cardiac Arrhythmias”, MJA, 179 (98-102)
16 Winter M E (2000), Basic clinical Pharmacokinetics, Applied Therapeutics, Inc
Vancouver, Washington, pp 7-102, 147-172
17 http://www.drugs.com/pro/theophylline.html
18 http://www.rxkinetics.com/theo.html
19 http://www.abbottdiagnostics.com/Science/pdf/learning_immunoassay_02.pdf
20 Charles F Lacy (2007), Drug Information Handbook, Lexicomp
21 Laurence Bruton et al (2008), Goodman & Gilman’s Manual of Pharmacology and
Therapeutics, Mc Graw Hill
Trang 7Phụ lục 1 Chương trình phần mềm GLOBALRPh.com hỗ trợ việc thực hiện TDM
của Aminoglycosid và Vancomycin
HOME BACK DRUG SEARCH DRUG TABLES DISCLAIMER *HEALTH TOPICS* PROFESSIONAL RESOURCE
Aminoglycoside-Vancomycin Dosing
This document Copyright © 2009 D.McAuley, GlobalRPh Inc All Rights Reserved.
Patient Name: Location: PROGRAM HINTS
Selecting the infusion time
Trang 8Sample recommendations for peak / trough concentrations
(Review levels) Gentamicin /
Tobramycin Amikacin Vancomycin
Infection Site Peak Trough Peak Trough Peak Trough
Vancomycin - Target trough levels??
M Goodwin, E Ashley Vancomycin: can we teach the mainstay of therapy for positives new tricks? Special to Infectious Disease News February 2006
Trang 9gram-http://www.infectiousdiseasenews.com/200602/frameset.asp?article=pharmconsult.asp Accessed: December 15th, 2006
"Independent of the reason, many clinicians are now targeting
higher troughs for vancomycin (from 15 to 20 µg/mL), especially
when treating more deep-seated infections (ie, meningitis,
endocarditis, osteomyelitis), in which vancomycin penetration may
also be an issue."
-
"The recent pneumonia guidelines, a joint publication from the
American Thoracic Society and the Infectious Diseases Society of
America (IDSA), advocate targeting higher vancomycin trough
concentrations Vancomycin is a large molecule, and we have
known for sometime that penetration into the lung and other
infection sites may be difficult Therefore, increasing the target
trough serum concentrations may result in higher pulmonary drug
concentrations The recommended target vancomycin trough in
these guidelines is 15 to 20 µg/mL However, there are no specific
data to say that troughs more than 15 µg/mL are associated with
improved outcomes over trough levels more than 5 or 10
µg/mL."
-
"Because many clinicians consider the vegetations involved in
endocarditis to be relatively difficult to penetrate, the traditional
target troughs were 15 to 20 µg/mL for this infection The recent
guidelines, however, recommend a lower trough concentration of 10
to 15 µg/mL As with the pneumonia guidelines, these targets
reflect the opinion of the expert panel in the absence of data to
document the ideal target."
See link above for the complete article
L Briceland Ask the Experts about Pharmacotherapy - From Medscape Pharmacists Would You Explain the Current Recommendations for Vancomycin Trough Levels? http://www.medscape.com/viewarticle/508120 Accessed: December 15th, 2006
"More recently, recommendations for optimal therapeutic serum
concentrations have varied widely: none at all except in select
clinical situations[3]; 5-10mcg/mL[2]; 5-15 mcg/mL[4]; and 5-20
mcg/mL.[5] These recommendations have arisen specifically due to
the lack of clear evidence for the concentrations needed to maintain therapeutic efficacy and avoid concentration-dependent toxicity[6]
Trang 10and the understanding that vancomycin exerts
concentration-independent killing."
"Exceeding the minimum inhibitory concentration (MIC) by 4-5 times does not produce further cidality; thus, the ranges cited would
provide adequate serum and tissue concentrations to kill most
pathogens (in which the MIC is generally less than 2 mcg/mL).[5]
The current dosing regimen of 15 mg/kg every 12 hours (in normal
renal function) is still employed with the intent of achieving
therapeutic troughs (now broadly defined as anywhere between
5-20 mcg/mL)." See link above for the complete article
Background information
Background information (Equations listed are calculated by the program)
Obtain baseline data:
Patient age, sex, height, weight, allergies, diagnosis, infection site, current
drug therapy, I/O's for past 24 hours, Tmax, WBC with diff, albumin,
Past medical history, Lab work-up: Scr, Bun, cultures etc.
Estimate Ideal body weight in (kg)
Males: IBW = 50 kg + 2.3 kg for each inch over 5 feet
Females: IBW = 45.5 kg + 2.3 kg for each inch over 5 feet.
If the actual body weight is greater than 25% of the calculated IBW, calculate the adjusted body weight (ABW):
ABW = IBW + 0.4(Total body weight - IBW)
Estimate Creatinine Clearance: (ml/min)
Cockcroft and Gault equation:
CrCl = [(140 - age) x IBW] / (Scr x 72) (x 0.85 for females)
Note: if the ABW (actual body weight) is less than the IBW use the
actual body weight for calculating the CRCL If the patient is >65yo and
creatinine<1, use 1 to calculate the creatinine clearance
Estimate kel (Elimination rate constant):
Amikacin /Gentamicin/Tobramycin: Kel = (0.00285 x CrCl) + 0.015
May also use: (0.003 x CrCl) + 0.01
Vancomycin: kel = (0.00083 x CRCL) + 0.0044 (used by program)
Trang 11Equation used by the Detroit VA Medical Center: CRCL x 0.0012
The above equations provide an estimate of the elimination rate constant based on population kinetics The following may decrease the usefulness of these equations:
*Renal failure, CHF, Burn patients, cystic fibrosis, severe hypotension, rapidly changing renal function (Burn victims and patients with cystic fibrosis usually have increased rates of elimination Patients with CHF or severe hypotension will have decreased rates of elimination due to decreased renal perfusion).
Estimate half-life (T1/2) in hours:
Select Time of Infusion (ti):
(a) Aminoglycosides: 30 minutes (0.5 hrs) (b) Vancomycin: 0-500 mg/ 0.5 hrs ; 501 to 1250 mg/ 1 hour ;
1251 to 1750/ 1.5 hrs ; >1750/ 2 hours
Calculate Dosing Interval (T) hrs
T = Ln (Cmax/Cmin) / kel + ti or estimated T = 3 x T1/2
Calculate Maintenance dose (MD): _mg
MD = [(kel) x (Vd) x (ti) x (Cpeak desired) x (1 - e-kT)] / (1 - e-kti)
or MD = (Cpeak desired) x Vd (eg: C = D/V, therefore D=C*V)
Calculate Predicted Peak and Trough at Steady State
Cmax = [Dose * 1-e-kti] / (kel)(Vd)(ti) 1-e-kT Cmin = Cmax * e-k(T-ti)
Trang 12Phụ lục 2.Chương trình phần mềm GLOBALRPh.com hỗ trợ thực hiện TDM của Digoxin
Digoxin Dosing Calculator
Determination of initial loading and maintanance dose
This document Copyright © 2006 GlobalRPh All Rights Reserved
Age: 70 | Male
| Scr(mg/dl): 1
Height: 70 Inches | Weight: 70 Kilograms
Select disease state: CHF
Enter desired Cpeak: 1.0
Dosage form: Tablets Acute CHF?
No
Interacting drugs: No interacting drugs
Dosing schedule Daily dosing
Submit
If steady state levels are available, use this table instead
Click here or program information
References:
Aronson JK: Clinical pharmacokinetics of cardiac glycosides in patients with renal dysfunction Clin Pharmacokinet 1983; 8:155-178
Behr ER, Veysey MJ, Berry D, Volans GN Optimum dose of
digoxin Lancet 1997 Jun 21;349(9068):1845
Bennett WM, Aronoff GR, Golper TA et al: Drug Prescribing in Renal Failure American College of Physicians, Philadelphia, PA, 1987
Cauffield JS, Gums JG, Grauer K The serum digoxin concentration:
Trang 13ten questions to ask Am Fam Physician 1997 Aug;56(2):495-503, 509-10
Cheng JW, Charland SL, Shaw LM, Kobrin S, Goldfarb S, Stanek EJ, Spinler SA Is the volume of distribution of digoxin reduced in patients with renal dysfunction? Determining digoxin pharmacokinetics by fluorescence polarization immunoassay Pharmacotherapy 1997 May-Jun;17(3):584-90
Fenster PE, Hager WD & Goodman MM:
Digoxin-quinidine-spironolactone interaction Clin Pharmacol Ther 1984; 36:70-73
Gilman AG, Rall TW, Nies AS et al (Eds): Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed Macmillan Publishing
Co, New York, NY, 1990
Hammerlein A, Derendorf H, Lowenthal DT Pharmacokinetic and pharmacodynamic changes in the elderly Clinical implications
Clin Pharmacokinet 1998 Jul;35(1):49-64
Hui J, Wang YM, Chandrasekaran A, Geraets DR, Caldwell JH,
Robertson LW, Reuning RH Disposition of tablet and capsule
formulations of digoxin in the elderly Pharmacotherapy 1994 Oct;14(5):607-12
Sep-Jelliffe, 1968; Product information Lanoxin (R), Glaxo Wellcome
Inc (Jelliffe RW: An improved method digoxin therapy Ann Intern Med 1968; 69:703.)
Jusko WJ, Szefler SJ & Goldfarb AL: Pharmacokinetic design of
digoxin dosage regimens in relation to renal function J Clin Pharmacol, 1974; 14:525-535
Koda-Kimble MA: Congestive heart failure, in Applied Therapeutics for Clinical Pharmacists, 2nd ed, edited by Koda-Kimble et al, Applied Therapeutics, Inc., San Francisco 1978; pp 161-86
Trang 14Kramer WG, Lewis RP, Cobb TC et al: Pharmacokinetics of digoxin:
comparison of a two and a three compartment model in man J Pharmacokinet Biopharm 1974; 2:299
Lee CH, Park YJ, Sands CD, Jones DW, Trang JM Bioavailability of digoxin tablets in healthy volunteers Arch Pharm Res 1994
Contact Privacy Policy Disclaimer
Copyright © 2005 GlobalRPh Inc.
Trang 15
Phụ lục 3 Chương trình Martindale calculators online center hỗ trợ việc thực hiện TDM
PHARMACOKINETIC DRUG DOSING
Pharmacokinetic dosing calculators, dosing charts, and graphic dosing tools are available for
aminoglycosides (amikacin, gentamicin, and tobramycin), Arixtra (fondaparinux), digoxin, lithium, theophylline, time above MIC and vancomycin The purpose of these tools is to prevent dosing errors due to hand calculations, standardize the process, and decrease the time required to calculate an appropriate regimen Other drug dosing calculators will be added as time permits
The dosing tools (charts, graphics and calculators) use standard non abbreviated pharmacokinetic dosing equations for a one compartment open model Simplified dosing equations are included below for those who wish to do hand calculations The calculators determine the patient's creatinine clearance, dosing weight, drug clearance, volume of distribution, dose per kg of dosing weight, and appropriate dosing regimen Their advantage is the lack of hand calculations and easy of use The calculators may be used to analyze serum levels too The graphic tools are faster and easier to use than traditional programs or the calculators when serum levels are being analyzed Ideally one can determine the initial regimen with the dosing calculator and then use the graphic tools for further dosage adjustments when pulse dosing aminoglycosides or dosing vancomycin
The Time Above MIC calculator compares the fraction of the dosing interval that drug levels are above the MIC for traditional short infusions of antibiotics displaying time depended killing (penicillins, cephalosporins, carbapenems) to more prolonged infusions Please read this review for more information You may export the file to excel and modify it as needed
If you have questions about the dosing tools contact Marshall Pierce
Arixtra P&T Review
Arixtra Dosing Protocol
Arixtra Monitoring Form
Arixtra Therapeutic Dosing Chart Based on Dosing Weight
Arixtra Therapeutic Dosing Chart Based on Known Serum Levels
Arixtra Prophylaxis Dosing Chart Based on Dosing Weight
Arixtra Prophylaxis Dosing Chart Based on Known Serum Levels
Arixtra Dosing Calculator and Data Fitting For Levels
Aminoglycosides Pulse Dosing: Pharmacy & Therapeutics Review
Amikacin Pulse Dosing Graphic Tool
Gentamicin & Tobramcyin Pulse Dosing Graphic Tool
Aminoglycoside Pulse Dosing Calculator and Data Fitting For Troughs
Aminoglycoside Traditional Dosing Calculator and Data Fitting for a Peak and Trough
Estimating Creatinine Clearance in Obese Patients: A Comparison of Salazar Corcoran versus Cockcroft Gault Equations The CG equation with a fat factor of 0.4 gives values 8-15% lower than
