Optimising Carboplatin Dose using Patient Characteristics and Therapeutic Drug Monitoring

Background: This analysis aimed to evaluate the impact of rivaroxaban exposure and patient characteristics on efficacy and safety outcomes in patients with acute coronary syndrome (ACS) and to determine whether therapeutic drug monitoring might provide additional information regarding rivaroxaban dose, beyond what patient characteristics provide. Methods: A post hoc exposure–response analysis was conducted using data from the phase III ATLAS ACS 2 Thrombolysis in Myocardial Infarction (TIMI) 51 study, in which 15,526 randomized ACS patients received rivaroxaban (2.5 mg or 5 mg twice daily) or placebo for a mean of 13 months (maximum follow up: 31 months). A multivariate Cox model was used to correlate individual predicted rivaroxaban exposures and patient characteristics with time-to-event clinical outcomes. Results: For the incidence of myocardial infarction (MI), ischemic stroke, or nonhemorrhagic cardiovascular death, hazard ratios (HRs) for steady-state maximum plasma concentration (Cmax) in the 5th and 95th percentiles versus the median were statistically significant but close to 1 for both rivaroxaban doses. For TIMI major bleeding events, a statistically significant association was observed with Cmax [HR, 1.08; 95% CI, 1.06–1.11 (95th percentile versus median, 2.5 mg twice daily)], sex [HR, 0.56; 95% CI, 0.38–0.84 (female versus male)], and previous revascularization [HR, 0.62; 95% CI, 0.44–0.87 (no versus yes)]. Conclusions: The shallow slopes of the exposure–response relationships and the lack of a clear therapeutic window render it unlikely that therapeutic drug monitoring in patients with ACS would provide additional information regarding rivaroxaban dose beyond that provided by patient characteristics.

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Therapeutic drug monitoring of drugs for treatment of substance-related disorders

European Psychiatry ◽

10.1016/s0924-9338(11)71724-2 ◽

2011 ◽

Vol 26 (S2) ◽

pp. 13-13

Author(s):

S. Brünen ◽

P.D. Vincent ◽

P. Baumann ◽

C. Hiemke ◽

U. Havemann-Reinecke

Keyword(s):

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Rating Scale ◽

Patient Characteristics ◽

Alcohol Dependency ◽

Therapeutic Drug ◽

Opioid Dependency ◽

Pharmacological Agents ◽

Literature Research ◽

Substance Related Disorders

IntroductionThe effect of pharmacotherapy of substance-related disorders is moderate at best.ObjectivesTherapeutic drug monitoring (TDM) could be an instrument to improve the outcomes. TDM is for most of these drugs not established yet.AimsThe authors built a literature based rating scale to evaluate the necessity of TDM for these pharmacological agents.MethodsA literature research was performed for TDM related properties of acamprosate, bupropion, buprenorphine, clomethiazole, disulfiram, methadone, naltrexone, and varenicline. A rating scale was established for evaluation. It included 28 items related to five categories (efficacy, toxicity, pharmacokinetics, patient characteristics and cost effectiveness). For comparison, three reference substances with established TDM were similarly assessed: clozapine, lithium and nortriptyline.ResultsThe three reference substances, lithium, clozapine and nortriptyline, achieved scores of 15, 18, and 14 points, respectively. Rating of methadone (19 points), bupropion (14 points), buprenorphine (14 points), disulfiram (13) and naltrexone (12 points in the indication opioid-dependency and 10 points in the indication alcohol dependency) achieved more than 30% of the reachable points, whereas acamprosate (9 points), clomethiazole (9 points), and varenicline (5 points) had fewer points especially in the main characteristics in favor of TDM.ConclusionsThese results suggest this rating scale is sensitive to detect the appropriateness of TDM for drug treatment. Literature based rating and clinical experience give evidence that TDM has the potential to optimize the pharmacotherapy of substance related-disorders with different rank orders of the single substances.

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Diagnose und Monitoring bei chronisch-entzündlicher Darmerkrankung

Therapeutische Umschau ◽

10.1024/0040-5930/a001002 ◽

2018 ◽

Vol 75 (5) ◽

pp. 316-328

Author(s):

Christian Ansprenger ◽

Emanuel Burri

Keyword(s):

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Morbus Crohn ◽

Therapeutic Drug ◽

Körperliche Untersuchung

Zusammenfassung. Die Diagnose und auch die Überwachung von chronisch entzündlichen Darmerkrankungen ruht auf mehreren Säulen: Anamnese, körperliche Untersuchung, Laborwerte (im Blut und Stuhl), Endoskopie, Histologie und Bildgebung. Die Diagnose kann nicht anhand eines einzelnen Befundes gestellt werden. In den letzten Jahren hat sich das Therapieziel weg von klinischen Endpunkten hin zu endoskopischen und sogar histologischen Endpunkten entwickelt. Für einige dieser neuen Therapieziele existiert allerdings noch keine allgemein gültige Definition. Regelmässige Endoskopien werden von Patienten schlecht toleriert, weshalb Surrogat-Marker wie Calprotectin untersucht wurden und eine gute Korrelation mit der mukosalen Entzündungsaktivität nachgewiesen werden konnte. Entsprechend zeigte sich bei Morbus Crohn eine Algorithmus-basierte Therapiesteuerung – unter anderem basierend auf Calprotectin – einer konventionellen Therapiesteuerung überlegen. Die Überwachung der medikamentösen Therapie («Therapeutic Drug Monitoring» [TDM]) ist ein zweites Standbein des Monitoring von chronisch entzündlichen Darmerkrankungen. Mit zunehmendem Einsatz vor allem der Biologika-Therapien wurden sowohl reaktives TDM (in Patienten mit klinischem Rezidiv) als auch proaktives TDM (in Patienten in Remission / stabiler Erkrankung) untersucht und haben (teilweise) Eingang in aktuelle Richtlinien gefunden. Zukünftige Studien werden die vorgeschlagenen Therapieziele besser definieren und den Nutzen der medikamentösen Therapieüberwachung auf den Krankheitsverlauf weiter untersuchen müssen.

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