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Pharmakokinetik, Pharmakodynamik, Interaktionen und Dosismodifikationen

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Kompendium Internistische Onkologie

Part of the book series: Springer Reference Medizin ((SRM))

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Zusammenfassung

Die Pharmakokinetik (PK) beschreibt das Verhalten eines Arzneimittels im menschlichen Körper, das im Wesentlichen aus den 4 Prozessen der Absorption, Distribution, Metabolismus und Elimination (ADME) besteht. Dabei werden Arzneimitteldosis, Verabreichungsmodus und Verabreichungsweg mit den im Körper gemessenen Konzentrationsverläufen mathematisch in Beziehung gesetzt. Die Pharmakodynamik (PD) untersucht die Beziehung zwischen Arzneimittelkonzentration und klinischem Effekt, also sowohl Wirkungen als auch Nebenwirkungen. Dabei kann eine evidente Beziehung zwischen Plasmakonzentration und klinischem Effekt bestehen, oder aber ein solcher Zusammenhang kann vollständig fehlen. Dosis-Wirkungs-Beziehungen bei der Verwendung von Onkologika sind nicht immer offensichtlich und teils nur gering oder moderat. Gründe dafür sind die zeitliche Verzögerung zwischen Arzneimittelverabreichung und klinischem Effekt, Abhängigkeit der Wirkung von der Biologie des jeweiligen Tumors, die Vielfalt möglicher unerwünschter Arzneimittelwirkungen oder die Verwendung von Wirkstoffkombinationen. Wirkstoffspezifische Eigenschaften von PK und PD haben einen großen Einfluss auf die Dosierung von Onkologika, beeinflussen das Wirkungs-Nebenwirkungs-Profil sowie Dosisanpassungen und sind deshalb für den Onkologen von Bedeutung.

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Literatur

  • Beumer JH, Chu E, Allegra C, Tanigawara Y, Milano G, Diasio R, Kim TW, Mathijssen RH, Zhang L, Arnold D, Muneoka K, Boku N, Joerger M (2019) Therapeutic drug monitoring in oncology: international association of therapeutic drug monitoring and clinical Toxicology recommendations for 5-fluorouracil therapy. Clin Pharmacol Ther 105(3):598–613

    Google Scholar 

  • Codacci-Pisanelli G, Pinedo HM, Lankelma J, Van Groeningen CJ, Van Kuilenburg AB, Van Gennip AH, Peters GJ (2005) Pharmacokinetics of bolus 5-fluorouracil: relationship between dose, plasma concentrations, area-under-the-curve and toxicity. J Chemother 17(3):315–320

    Article  CAS  Google Scholar 

  • Cortes JE, Egorin MJ, Guilhot F, Molimard M, Mahon FX (2009) Pharmacokinetic/pharmacodynamic correlation and blood-level testing in imatinib therapy for chronic myeloid leukemia. Leukemia 23(9):1537–1544

    Article  CAS  Google Scholar 

  • Danesi R, Fogli S, Gennari A, Conte P, Del Tacca M (2002) Pharmacokinetic-pharmacodynamic relationships of the anthracycline anticancer drugs. Clin Pharmacokinet 41(6):431–444

    Article  CAS  Google Scholar 

  • Duffull SB, Robinson BA (1997) Clinical pharmacokinetics and dose optimisation of carboplatin. Clin Pharmacokinet 33(3):161–183

    Article  CAS  Google Scholar 

  • Gamelin E, Delva R, Jacob J, Merrouche Y, Raoul JL, Pezet D, Dorval E, Piot G, Morel A, Boisdron-Celle M (2008) Individual fluorouracil dose adjustment based on pharmacokinetic follow-up compared with conventional dosage: results of a multicenter randomized trial of patients with metastatic colorectal cancer. J Clin Oncol 26(13):2099–2105

    Article  CAS  Google Scholar 

  • Houk BE, Bello CL, Poland B, Rosen LS, Demetri GD, Motzer RJ (2010) Relationship between exposure to sunitinib and efficacy and tolerability endpoints in patients with cancer: results of a pharmacokinetic/pharmacodynamic meta-analysis. Cancer Chemother Pharmacol 66(2):357–371

    Article  CAS  Google Scholar 

  • Joerger M, Schellens JH, Beijnen JH (2004) Therapeutic drug monitoring of non-anticancer drugs in cancer patients. Methods Find Exp Clin Pharmacol 26(7):531–545

    Article  CAS  Google Scholar 

  • Joerger M, Huitema AD, Richel DJ, Dittrich C, Pavlidis N, Briasoulis E, Vermorken JB, Strocchi E, Martoni A, Sorio R, Sleeboom HP, Izquierdo MA, Jodrell DI, Calvert H, Boddy AV, Hollema H, Fety R, Van der Vijgh WJ, Hempel G, Chatelut E, Karlsson M, Wilkins J, Tranchand B, Schrijvers AH, Twelves C, Beijnen JH, Schellens JH (2007) Population pharmacokinetics and pharmacodynamics of paclitaxel and carboplatin in ovarian cancer patients: a study by the European organization for research and treatment of cancer-pharmacology and molecular mechanisms group and new drug development group. Clin Cancer Res 13(21):6410–6418

    Article  CAS  Google Scholar 

  • Joerger M, Huitema AD, Krahenbuhl S, Schellens JH, Cerny T, Reni M, Zucca E, Cavalli F, Ferreri AJ (2010) Methotrexate area under the curve is an important outcome predictor in patients with primary CNS lymphoma: A pharmacokinetic-pharmacodynamic analysis from the IELSG no. 20 trial. Br J Cancer 102(4):673–677

    Article  CAS  Google Scholar 

  • Joerger M, von Pawel J, Kraff S, Fischer JR, Eberhardt W, Gauler TC, Mueller L, Reinmuth N, Reck M, Kimmich M, Mayer F, Kopp HG, Behringer DM, Ko YD, Hilger RA, Roessler M, Kloft C, Henrich A, Moritz B, Miller MC, Salamone SJ, Jaehde U (2016) Open-label, randomized study of individualized, pharmacokinetically (PK)-guided dosing of paclitaxel combined with carboplatin or cisplatin in patients with advanced non-small-cell lung cancer (NSCLC). Ann Oncol 27(10):1895–1902

    Article  CAS  Google Scholar 

  • Jonge ME de, Huitema AD, Schellens JH, Rodenhuis S, Beijnen JH (2005) Individualised cancer chemotherapy: strategies and performance of prospective studies on therapeutic drug monitoring with dose adaptation: a review. Clin Pharmacokinet 44(2):147–173

    Google Scholar 

  • Jonge ME de, Huitema AD, Beijnen JH, Rodenhuis S (2006) High exposures to bioactivated cyclophosphamide are related to the occurrence of veno-occlusive disease of the liver following high-dose chemotherapy. Br J Cancer 94(9):1226–1230

    Google Scholar 

  • Moore MJ, Erlichman C (1987) Therapeutic drug monitoring in oncology. Problems and potential in antineoplastic therapy. Clin Pharmacokinet 13(4):205–227

    Article  CAS  Google Scholar 

  • Nagai N, Kinoshita M, Ogata H, Tsujino D, Wada Y, Someya K, Ohno T, Masuhara K, Tanaka Y, Kato K, Nagai H, Yokoyama A, Kurita Y (1996) Relationship between pharmacokinetics of unchanged cisplatin and nephrotoxicity after intravenous infusions of cisplatin to cancer patients. Cancer Chemother Pharmacol 39(1–2):131–137

    Article  CAS  Google Scholar 

  • Newell DR (1994) Can pharmacokinetic and pharmacodynamic studies improve cancer chemotherapy? Ann Oncol 5(Suppl 4):9–14; discussion 15

    Article  Google Scholar 

  • Perez C, Wang YM, Sutow WW, Herson J (1978) Significance of the 48-hour plasma level in high-dose methotrexate regimens. Cancer Clin Trials 1(2):107–111

    CAS  PubMed  Google Scholar 

  • Petros WP, Broadwater G, Berry D, Jones RB, Vredenburgh JJ, Gilbert CJ, Gibbs JP, Colvin OM, Peters WP (2002) Association of high-dose cyclophosphamide, cisplatin, and carmustine pharmacokinetics with survival, toxicity, and dosing weight in patients with primary breast cancer. Clin Cancer Res 8(3):698–705

    CAS  PubMed  Google Scholar 

  • Ratain MJ, Schilsky RL, Choi KE, Guarnieri C, Grimmer D, Vogelzang NJ, Senekjian E, Liebner MA (1989) Adaptive control of etoposide administration: impact of interpatient pharmacodynamic variability. Clin Pharmacol Ther 45(3):226–233

    Article  CAS  Google Scholar 

  • Ratain MJ, Schilsky RL, Conley BA, Egorin MJ (1990) Pharmacodynamics in cancer therapy. J Clin Oncol 8(10):1739–1753

    Article  CAS  Google Scholar 

  • Rousseau A, Marquet P, Debord J, Sabot C, Lachatre G (2000) Adaptive control methods for the dose individualisation of anticancer agents. Clin Pharmacokinet 38(4):315–353

    Article  CAS  Google Scholar 

  • Schiller M, Hohenlochter B, Schulze-Westhoff P, Zimmermann M, Ritter J, Jurgens H, Boos J (1996) Intracellular retention of cytarabine-triphosphate (Ara-CTP) in blasts of children with acute lymphoblastic leukemia. Correlation with clinical course parameters. Klin Padiatr 208(4):151–159

    Article  CAS  Google Scholar 

  • Stewart CF, Arbuck SG, Fleming RA, Evans WE (1991) Relation of systemic exposure to unbound etoposide and hematologic toxicity. Clin Pharmacol Ther 50(4):385–393

    Article  CAS  Google Scholar 

  • Warmerdam LJ van, Rodenhuis S, van der Wall E, Maes RA, Beijnen JH (1996) Pharmacokinetics and pharmacodynamics of carboplatin administered in a high-dose combination regimen with thiotepa, cyclophosphamide and peripheral stem cell support. Br J Cancer 73(8):979–984

    Google Scholar 

  • Whitehead VM, Vuchich MJ, Cooley LD, Lauer SJ, Mahoney DH, Shuster JJ, Payment C, Koch PA, Akabutu JJ, Bowen T, Kamen BA, Ravindranath Y, Emami A, Look AT, Beardsley GP, Pullen DJ, Camitta B (1998) Accumulation of methotrexate polyglutamates, ploidy and trisomies of both chromosomes 4 and 10 in lymphoblasts from children with B-progenitor cell acute lymphoblastic leukemia: a Pediatric Oncology Group Study. Leuk Lymphoma 31(5-6):507–519

    Article  CAS  Google Scholar 

  • Zandvliet AS, Schellens JH, Beijnen JH, Huitema AD (2008) Population pharmacokinetics and pharmacodynamics for treatment optimization in clinical oncology. Clin Pharmacokinet 47(8):487–513

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Kantonsspital St. Gallen, St. Gallen, Schweiz

    Markus Joerger

  2. Institute of Pharmacy, Clinical Pharmacy, Universität Greifswald, Greifswald, Deutschland

    Christoph Ritter

  3. Berlin, Deutschland

    Susen Burock

Authors
  1. Markus Joerger
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  2. Christoph Ritter
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  3. Susen Burock
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Correspondence to Markus Joerger .

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Editors and Affiliations

  1. Abt. Hämatologie und Onkologie, Universitätsklinikum Halle-Wittenberg Klinik und Poliklinik Innere Medizin IV, Halle, Sachsen-Anhalt, Deutschland

    Hans-Joachim Schmoll

Section Editor information

  1. Institute of Pharmacy, Clinical Pharmacy, Universität Greifswald, Greifswald, Mecklenburg-West Pomerania, Deutschland

    Christoph Ritter

  2. Berlin, Deutschland

    Susen Burock

  3. Berlin, Germany

    Ulrich Keilholz

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Joerger, M., Ritter, C., Burock, S. (2022). Pharmakokinetik, Pharmakodynamik, Interaktionen und Dosismodifikationen. In: Schmoll, HJ. (eds) Kompendium Internistische Onkologie . Springer Reference Medizin. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-46764-0_272-1

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  • DOI: https://doi.org/10.1007/978-3-662-46764-0_272-1

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