title: A new frontier in haematology - combining pharmacokinetic with pharmacodynamic factors to improve choice and dose of drug.
abstract: The issue of tailored dosing adjusted according to a range of patient-specific factors other than bodyweight or body surface area is of large and increasing clinical and financial concern. Even if it is known that dosing alterations are likely to be required for parameters such as body composition, gender and pharmacogenetics, the amount of dosing change is unknown. Thus, pharmacokinetically guided dosing is making a resurgence, particularly in areas of medicine where there are cost constraints or safety issues, such as in haematology medications. However, the evidence to support the behaviour is minimal, particularly when long-term outcomes are considered. In haematology, there are particular issues around efficacy, toxicity and overall cost. Newer targeted agents, such as the monoclonal antibody rituximab and the tyrosine kinase inhibitor imatinib, whilst clearly being highly effective, are dosed on a milligram per square metre (rituximab) or fixed dose basis (imatinib), regardless of body composition, tumour aspects or comorbidity. This review questions this practice and raises important clinical issues; specifically, the clinical potential for combined pharmacokinetically and pharmacodynamically guided dosing of new targeted agents in haematological malignancies. This pharmacokinetically and pharmacodynamically guided dosing is an emerging area of clinical pharmacology, driven predominantly by toxicity, efficacy and cost issues, but also because reasonable outcomes are being noted with more appropriately dosed older medications adjusted for patient-specific factors. Clinical trials to investigate the optimization of rituximab dose scheduling are required.
authors.affiliation: School of Medicine, University of Queensland, Princess Alexandra Hospital Campus, Woolloongabba, Australia; Translational Research Institute, Woolloongabba, Queensland, Australia.
authors.forename: David Rey
authors.initials: DR
authors.lastname: Arpon
authors.forename: Maher K
authors.initials: MK
authors.lastname: Gandhi
authors.forename: Jennifer H
authors.initials: JH
authors.lastname: Martin
mesh_terms: D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D001549:Benzamides / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D003657:Decision Making; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D019337:Hematologic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D000068877:Imatinib Mesylate; D008954:Models, Biological; D058990:Molecular Targeted Therapy; D010879:Piperazines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D057285:Precision Medicine; D011743:Pyrimidines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D000069283:Rituximab; D012737:Sex Factors
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000069283:Rituximab; D000068877:Imatinib Mesylate
keywords: haematology; imatinib; pharmacodynamics; pharmacokinetics; rituximab