Last updated 17 June 2024
Medicine |
Use |
Target (see Target
Types) |
Method |
References |
Busulfan |
Conditioning regimen before bone marrow
transplantation (neonates to adults) |
Prediction of
dose required to achieve the target. Target choice of 1. Average
steady state concentration mg/L (Css
avg) umol/L (Css avg) 2. AUC at
steady state with user specified target dosing interval umol/L*min (AUCssDI) mg/L*h (AUCssDI) 3. Cumulative
AUC over user selected interval mg/L*h (cum
AUC 4 days) mg/L*h (cum
AUC 2 days) |
Dose predictions from trapezoidal AUC and
Bayesian estimates of
PK parameters. |
Holford & Holford (1),
Holford (2) |
Gentamicin |
Any indication for which gentamicin is
administered intravenously (neonates to adults) |
Prediction of
dose required to achieve the target. Target choice of 1. Steady
state average concentration mg/L (Css
avg) 2. Steady
state AUC with user specified dosing interval mg/L*h
(AUCssDI) 3. Steady
state concentration mg/L (Css1h) mg/L (Css2h) mg/L (Css4h) mg/L (Css8h) mg/L (Css12h) mg/L (Css24h) mg/L
(Csstrough) |
Dose predictions from trapezoidal AUC and
Bayesian estimates of
PK parameters |
Holford & Holford (1),
Holford (2),
Holford et al. (3) |
Tobramycin |
Any indication for which tobramycin is
administered intravenously (neonates to adults) |
Prediction of
dose required to achieve the target. Target choice of 1. Steady
state average concentration mg/L (Css
avg) 2. Steady
state AUC with user specified dosing interval mg/L*h
(AUCssDI) 3. Steady
state concentration mg/L (Css1h) mg/L (Css2h) mg/L (Css4h) mg/L (Css8h) mg/L (Css12h) mg/L (Css24h) mg/L
(Csstrough) |
Dose predictions from trapezoidal AUC and
Bayesian estimates of PK parameters |
Holford & Holford (1),
Holford (2) |
Vancomycin |
Any indication for which vancomycin is
administered intravenously (neonates to adults) |
Prediction of
dose required to achieve the target. Target choice of 1. Average
steady state concentration mg/L (Css
avg) 2. AUC at
steady state with user specified dosing interval mg/L*h
(AUCss24) mg/L*h
(AUCssDI) 3. Steady
state concentration mg/L (Css1h) mg/L (Css2h) mg/L (Css4h) mg/L (Css8h) mg/L (Css12h) mg/L (Css24h) mg/L
(Csstrough) |
Dose predictions from trapezoidal AUC and
Bayesian estimates of PK parameters |
Holford & Holford (1),
Holford (2), Holford et al. (3), Ma et al.(4) |
Amikacin |
Any indication for which amikacin is
administered intravenously (neonates to adults) |
Prediction of
dose required to achieve the target. Target choice of 1. Steady
state average concentration mg/L (Css
avg) 2. Steady
state AUC with user specified dosing interval mg/L*h
(AUCssDI) 3. Steady
state concentration mg/L (Css1h) mg/L (Css2h) mg/L (Css4h) mg/L (Css8h) mg/L (Css12h) mg/L (Css24h) mg/L
(Csstrough) |
Dose predictions from trapezoidal AUC and
Bayesian estimates of PK parameters |
Holford & Holford (1),
Holford (2), Holford
et al. (3) |
Methotrexate |
High dose methotrexate e.g. acute lymphoblastic
leukemia (age> 2y) |
Prediction of
dose required to achieve the target AUC0-inf after a dose umol * h
(AUC0-inf) |
Dose predictions from trapezoidal AUC and
Bayesian estimates of clearance. |
Holford & Holford (1),
Holford (2),
Holford et al. (5) |
Warfarin |
Oral anticoagulation (age > 2y) |
Prediction of
dose required to achieve the target average steady state INR |
Dose predictions Bayesian estimates of PK and PD
parameters |
Holford & Holford (1),
Holford (2) |
Voriconazole |
Any indication for which voriconazole is
administered intravenously (age> 2y) |
Prediction of
dose required to achieve the target. Target choice of 1. Average
steady state concentration (mg/L)/(mg/L)
CssAvg/MIC 2. Steady
state trough concentration (mg/L)/(mg/L)
CssTrough (Css12h/MIC) (mg/L)/(mg/L)
CssTroughDI/MIC) |
Dose predictions from trapezoidal AUC and
Bayesian estimates of PK parameters |
Holford & Holford (1),
Holford (2) |
Linezolid |
Any indication for which linezolid is
administered intravenously or orally (age> 2y) |
Prediction of
dose required to achieve the target AUC at steady state with user specified
dosing interval. h
(AUCssDI/MIC) |
Dose predictions from trapezoidal AUC and
Bayesian estimates of PK parameters |
Holford & Holford (1),
Holford (2) |
Dabigatran |
Oral anticoagulation (age > 2y) |
Prediction of
dose required to achieve the target average steady state concentration mg/L (Css
avg) |
Dose predictions from trapezoidal AUC and
Bayesian estimates of PK parameters |
Holford & Holford (1),
Holford (2) |
Caffeine |
Apnea of prematurity (neonates) |
Prediction of
dose required to achieve the target average steady state concentration mg/L (Css
avg) |
Dose predictions from trapezoidal AUC and
Bayesian estimates of PK parameters |
Holford & Holford (1),
Holford et al (6) |
Hydroxychloroquine |
Anti-inflammatory indications (age> >2 y) |
Prediction of
dose required to achieve the target average steady state concentration mg/L (Css
avg) |
Dose predictions from trapezoidal AUC and
Bayesian estimates of PK parameters |
Holford & Holford (1),
Holford (2) |
Posaconazole |
Any indication for which posaconazole is
administered orally (infants to adults) |
Prediction of
dose required to achieve the target. Target choice of 1. Average
steady state concentration (mg/L) CssAvg
2. Steady
state trough concentration (mg/L) (Css8h,
Css12h) |
Dose predictions from trapezoidal AUC and
Bayesian estimates of PK parameters |
Holford & Holford (1),
Holford (2) |
References:
1. Holford N, Holford SD. NextDose (www.nextdose.org) a web-based collaborative tool for concentration guided dosing using the target concentration intervention approach 2024 [
2. Holford NHG. NextDose A web based dosing tool Development version 2017. PAGANZ 2017 https://wwwpaganzorg/abstracts/nextdose-a-web-based-dosing-tool-development-version-2017/. 2017;Accessed 20 Feb 2017.
3. Holford N, O'Hanlon CJ, Allegaert K, Anderson B, Falcγo A, Simon N, et al. A physiological approach to renal clearance: From premature neonates to adults. Br J Clin Pharmacol. 2024;90(4):1066-80.
4. Ma G, Holford N, Hannam J, Harrison J. Vancomycin Target Concentration Intervention vs. Therapeutic Drug Monitoring. ASCEPT-PAGANZ; Queenstown2019.
5. Holford NHG, Hirankarn S, Dombrowsky E, Patel D, Barrett JS. What is the between cycle variability in methotrexate clearance? PAGE. 2012;21 (Abstr 2474):[www.page-meeting.org/?abstract=2474].
6. Holford N, Yang X, Jiang Z, Shen H, Shi J, Shu X, et al. Rational dosing of caffeine using target concentration intervention to improve treatment of apnea of prematurity Abstr 9027 [www.page-meeting.org/?abstract=9027]. PAGE. 2019;28.