T M A Kerkhofs1, L J J Derijks2, M H T Ettaieb2, E M W Eekhoff2, C Neef3, H Gelderblom2, J den Hartigh2, H J Guchelaar2, H R Haak4. 1. Department of Internal MedicineMáxima Medical Center, Ds. Th. Fliednerstraat 1, Eindhoven/Veldhoven 5631, The NetherlandsDepartment of Clinical PharmacologyMáxima Medical Center, Eindhoven/Veldhoven, The NetherlandsSection EndocrinologyDepartment of Internal Medicine, VU Medical Center, Vrije Universiteit Amsterdam, Amsterdam, The NetherlandsDepartment of Clinical Pharmacy and ToxicologyMaastricht University Medical Center+, Maastricht, The NetherlandsDepartment of Health Services Research and CAPHRI School for Public Health and Primary CareMaastricht University, Maastricht, The NetherlandsDepartments of Clinical OncologyClinical Pharmacy and ToxicologyLeiden University Medical Center, Leiden, The NetherlandsDivision of General Internal MedicineDepartment of Internal Medicine, Maastricht University Medical Centre+, Maastricht, The Netherlands T.Kerkhofs@mmc.nl. 2. Department of Internal MedicineMáxima Medical Center, Ds. Th. Fliednerstraat 1, Eindhoven/Veldhoven 5631, The NetherlandsDepartment of Clinical PharmacologyMáxima Medical Center, Eindhoven/Veldhoven, The NetherlandsSection EndocrinologyDepartment of Internal Medicine, VU Medical Center, Vrije Universiteit Amsterdam, Amsterdam, The NetherlandsDepartment of Clinical Pharmacy and ToxicologyMaastricht University Medical Center+, Maastricht, The NetherlandsDepartment of Health Services Research and CAPHRI School for Public Health and Primary CareMaastricht University, Maastricht, The NetherlandsDepartments of Clinical OncologyClinical Pharmacy and ToxicologyLeiden University Medical Center, Leiden, The NetherlandsDivision of General Internal MedicineDepartment of Internal Medicine, Maastricht University Medical Centre+, Maastricht, The Netherlands. 3. Department of Internal MedicineMáxima Medical Center, Ds. Th. Fliednerstraat 1, Eindhoven/Veldhoven 5631, The NetherlandsDepartment of Clinical PharmacologyMáxima Medical Center, Eindhoven/Veldhoven, The NetherlandsSection EndocrinologyDepartment of Internal Medicine, VU Medical Center, Vrije Universiteit Amsterdam, Amsterdam, The NetherlandsDepartment of Clinical Pharmacy and ToxicologyMaastricht University Medical Center+, Maastricht, The NetherlandsDepartment of Health Services Research and CAPHRI School for Public Health and Primary CareMaastricht University, Maastricht, The NetherlandsDepartments of Clinical OncologyClinical Pharmacy and ToxicologyLeiden University Medical Center, Leiden, The NetherlandsDivision of General Internal MedicineDepartment of Internal Medicine, Maastricht University Medical Centre+, Maastricht, The Netherlands Department of Internal MedicineMáxima Medical Center, Ds. Th. Fliednerstraat 1, Eindhoven/Veldhoven 5631, The NetherlandsDepartment of Clinical PharmacologyMáxima Medical Center, Eindhoven/Veldhoven, The NetherlandsSection EndocrinologyDepartment of Internal Medicine, VU Medical Center, Vrije Universiteit Amsterdam, Amsterdam, The NetherlandsDepartment of Clinical Pharmacy and ToxicologyMaastricht University Medical Center+, Maastricht, The NetherlandsDepartment of Health Services Research and CAPHRI School for Public Health and Primary CareMaastricht University, Maastricht, The NetherlandsDepartments of Clinical OncologyClinical Pharmacy and ToxicologyLeiden University Medical Center, Leiden, The NetherlandsDivision of General Internal MedicineDepartment of Internal Medicine, Maastricht University Medical Centre+, Maastricht, The Netherlands. 4. Department of Internal MedicineMáxima Medical Center, Ds. Th. Fliednerstraat 1, Eindhoven/Veldhoven 5631, The NetherlandsDepartment of Clinical PharmacologyMáxima Medical Center, Eindhoven/Veldhoven, The NetherlandsSection EndocrinologyDepartment of Internal Medicine, VU Medical Center, Vrije Universiteit Amsterdam, Amsterdam, The NetherlandsDepartment of Clinical Pharmacy and ToxicologyMaastricht University Medical Center+, Maastricht, The NetherlandsDepartment of Health Services Research and CAPHRI School for Public Health and Primary CareMaastricht University, Maastricht, The NetherlandsDepartments of Clinical OncologyClinical Pharmacy and ToxicologyLeiden University Medical Center, Leiden, The NetherlandsDivision of General Internal MedicineDepartment of Internal Medicine, Maastricht University Medical Centre+, Maastricht, The Netherlands Department of Internal MedicineMáxima Medical Center, Ds. Th. Fliednerstraat 1, Eindhoven/Veldhoven 5631, The NetherlandsDepartment of Clinical PharmacologyMáxima Medical Center, Eindhoven/Veldhoven, The NetherlandsSection EndocrinologyDepartment of Internal Medicine, VU Medical Center, Vrije Universiteit Amsterdam, Amsterdam, The NetherlandsDepartment of Clinical Pharmacy and ToxicologyMaastricht University Medical Center+, Maastricht, The NetherlandsDepartment of Health Services Research and CAPHRI School for Public Health and Primary CareMaastricht University, Maastricht, The NetherlandsDepartments of Clinical OncologyClinical Pharmacy and ToxicologyLeiden University Medical Center, Leiden, The NetherlandsDivision of General Internal MedicineDepartment of Internal Medicine, Maastricht University Medical Centre+, Maastricht, The Netherlands Department of Internal MedicineMáxima Medical Center, Ds. Th. Fliednerstraat 1, Eindhoven/Veldhoven 5631, The NetherlandsDepartment of Clinical PharmacologyMáxima Medical Center, Eindhoven/Veldhoven, The NetherlandsSection EndocrinologyDepartment of Internal Medicine, VU Medical Cent
Abstract
OBJECTIVE: Mitotane is the drug of choice in patients with adrenocortical carcinoma. The anti-neoplastic effect is correlated with mitotane plasma levels, which render it crucial to reach and maintain the concentration above 14 mg/l. However, mitotane pharmacokinetics is poorly understood. The aim of this study was to investigate the variation in plasma mitotane levels during the day and the influence of a single morning dose. DESIGN: A prospective case-control study was conducted to investigate the variation in plasma mitotane levels. METHODS: Patients who had been treated for at least 24 weeks and had reached the therapeutic plasma level (14 mg/l) at least once were eligible. In the first group, mitotane levels were determined hourly for the duration of 8 h after administration of a single morning dose. In the second group, mitotane levels were assessed similarly without administration of a morning dose. RESULTS: Ten patients were included in this study, and three patients participated in both groups. Median plasma level at baseline was 16.2 mg/l (range 11.3-23.3 mg/l) in the first group (n=7) and 17.0 mg/l (13.7-23.8) in the second group (n=6). Plasma levels displayed a median increase compared with baseline of 24% (range 6-42%) at t=4 after morning dose and a change of 13% (range -14 to 33%) at t=4 without morning dose (P=0.02). CONCLUSION: A substantial increase in mitotane plasma levels was observed in steady-state patients within a period of 8 h after morning dosing. Without morning dose, mitotane curves showed a variable profile throughout the day. This implies that random sampling could yield incidentally high levels. For this reason, we recommend early-morning trough sampling as standard management in monitoring mitotane treatment.
OBJECTIVE:Mitotane is the drug of choice in patients with adrenocortical carcinoma. The anti-neoplastic effect is correlated with mitotane plasma levels, which render it crucial to reach and maintain the concentration above 14 mg/l. However, mitotane pharmacokinetics is poorly understood. The aim of this study was to investigate the variation in plasma mitotane levels during the day and the influence of a single morning dose. DESIGN: A prospective case-control study was conducted to investigate the variation in plasma mitotane levels. METHODS:Patients who had been treated for at least 24 weeks and had reached the therapeutic plasma level (14 mg/l) at least once were eligible. In the first group, mitotane levels were determined hourly for the duration of 8 h after administration of a single morning dose. In the second group, mitotane levels were assessed similarly without administration of a morning dose. RESULTS: Ten patients were included in this study, and three patients participated in both groups. Median plasma level at baseline was 16.2 mg/l (range 11.3-23.3 mg/l) in the first group (n=7) and 17.0 mg/l (13.7-23.8) in the second group (n=6). Plasma levels displayed a median increase compared with baseline of 24% (range 6-42%) at t=4 after morning dose and a change of 13% (range -14 to 33%) at t=4 without morning dose (P=0.02). CONCLUSION: A substantial increase in mitotane plasma levels was observed in steady-state patients within a period of 8 h after morning dosing. Without morning dose, mitotane curves showed a variable profile throughout the day. This implies that random sampling could yield incidentally high levels. For this reason, we recommend early-morning trough sampling as standard management in monitoring mitotane treatment.
Authors: Lauren M Postlewait; Cecilia G Ethun; Thuy B Tran; Jason D Prescott; Timothy M Pawlik; Tracy S Wang; Jason Glenn; Ioannis Hatzaras; Rivfka Shenoy; John E Phay; Kara Keplinger; Ryan C Fields; Linda X Jin; Sharon M Weber; Ahmed Salem; Jason K Sicklick; Shady Gad; Adam C Yopp; John C Mansour; Quan-Yang Duh; Natalie Seiser; Carmen C Solorzano; Colleen M Kiernan; Konstantinos I Votanopoulos; Edward A Levine; Charles A Staley; George A Poultsides; Shishir K Maithel Journal: J Am Coll Surg Date: 2015-12-21 Impact factor: 6.113
Authors: Nada El Ghorayeb; Geneviève Rondeau; Mathieu Latour; Christian Cohade; Harold Olney; André Lacroix; Paul Perrotte; Alexis Sabourin; Tania L Mazzuco; Isabelle Bourdeau Journal: Medicine (Baltimore) Date: 2016-03 Impact factor: 1.889
Authors: Rosa Maria Paragliola; Francesco Torino; Giampaolo Papi; Pietro Locantore; Alfredo Pontecorvi; Salvatore Maria Corsello Journal: Eur Endocrinol Date: 2018-09-10