TY  - JOUR
A1  - Mueller-Schoell, Anna
A1  - Groenland, Stefanie L.
A1  - Scherf-Clavel, Oliver
A1  - van Dyk, Madele
A1  - Huisinga, Wilhelm
A1  - Michelet, Robin
A1  - Jaehde, Ulrich
A1  - Steeghs, Neeltje
A1  - Huitema, Alwin D. R.
A1  - Kloft, Charlotte
T1  - Therapeutic drug monitoring of oral targeted antineoplastic drugs
JF  - European journal of clinical pharmacology
N2  - Purpose This review provides an overview of the current challenges in oral targeted antineoplastic drug (OAD) dosing and outlines the unexploited value of therapeutic drug monitoring (TDM). Factors influencing the pharmacokinetic exposure in OAD therapy are depicted together with an overview of different TDM approaches. Finally, current evidence for TDM for all approved OADs is reviewed. Methods A comprehensive literature search (covering literature published until April 2020), including primary and secondary scientific literature on pharmacokinetics and dose individualisation strategies for OADs, together with US FDA Clinical Pharmacology and Biopharmaceutics Reviews and the Committee for Medicinal Products for Human Use European Public Assessment Reports was conducted. Results OADs are highly potent drugs, which have substantially changed treatment options for cancer patients. Nevertheless, high pharmacokinetic variability and low treatment adherence are risk factors for treatment failure. TDM is a powerful tool to individualise drug dosing, ensure drug concentrations within the therapeutic window and increase treatment success rates. After reviewing the literature for 71 approved OADs, we show that exposure-response and/or exposure-toxicity relationships have been established for the majority. Moreover, TDM has been proven to be feasible for individualised dosing of abiraterone, everolimus, imatinib, pazopanib, sunitinib and tamoxifen in prospective studies. There is a lack of experience in how to best implement TDM as part of clinical routine in OAD cancer therapy. Conclusion Sub-therapeutic concentrations and severe adverse events are current challenges in OAD treatment, which can both be addressed by the application of TDM-guided dosing, ensuring concentrations within the therapeutic window.
KW  - targeted antineoplastic drugs
KW  - tyrosine kinase inhibitors
KW  - therapeutic
KW  - drug monitoring
KW  - oral anticancer drugs
KW  - personalised medicine
Y1  - 2020
U6  - https://doi.org/10.1007/s00228-020-03014-8
SN  - 0031-6970
SN  - 1432-1041
VL  - 77
IS  - 4
SP  - 441
EP  - 464
PB  - Springer
CY  - Heidelberg
ER  - 
TY  - JOUR
A1  - Chung, Oliver
A1  - Vongpatanasin, Wanpen
A1  - Bonaventura, Klaus
A1  - Lotan, Yair
A1  - Sohns, Christian
A1  - Haverkamp, Wilhelm
A1  - Dorenkamp, Marc
T1  - Potential cost-effectiveness of therapeutic drug monitoring in patients with resistant hypertension
JF  - Journal of hypertension
N2  - Background: Nonadherence to drug therapy poses a significant problem in the treatment of patients with presumed resistant hypertension. It has been shown that therapeutic drug monitoring (TDM) is a useful tool for detecting nonadherence and identifying barriers to treatment adherence, leading to effective blood pressure (BP) control. However, the cost-effectiveness of TDM in the management of resistant hypertension has not been investigated.
 Results: In the age group of 60-year olds, TDM gained 1.07 QALYs in men and 0.97 QALYs in women at additional costs of (sic)3854 and (sic)3922, respectively. Given a willingness-to-pay threshold of (sic)35 000 per QALY gained, the probability of TDM being cost-effective was 95% or more in all age groups from 30 to 90 years. Results were influenced mostly by the frequency of TDM testing, the rate of nonresponders to TDM, and the magnitude of effect of TDM on BP.
 Conclusion: Therapeutic drug monitoring presents a potential cost-effective healthcare intervention in patients diagnosed with resistant hypertension. Importantly, this finding is valid for a wide range of patients, independent of sex and age.
KW  - cardiovascular diseases
KW  - cost and cost analysis
KW  - cost-benefit analysis
KW  - drug monitoring
KW  - hypertension
KW  - medication adherence
KW  - probability
KW  - risk assessment
Y1  - 2014
U6  - https://doi.org/10.1097/HJH.0000000000000346
SN  - 0263-6352
SN  - 1473-5598
VL  - 32
IS  - 12
SP  - 2411
EP  - 2421
PB  - Lippincott Williams & Wilkins
CY  - Philadelphia
ER  -