title: Bleomycin pharmacokinetics of bolus bleomycin dose in elderly cancer patients treated with electrochemotherapy.
abstract: With the aim to determine effective therapeutic window of electrochemotherapy, we analyzed bleomycin pharmacokinetic parameters in elderly patients.
  
  
  
  In prospective clinical study in the treatment of tumors with electrochemotherapy, blood samples of patients older than 65 years were collected after the bolus intravenous injection of bleomycin (15,000 IU/m(2)). In serum samples, quantitative analysis was performed with liquid chromatography coupled to high-resolution mass spectrometry. Based on the data, the pharmacokinetic parameters of bleomycin elimination were determined.
  
  
  
  Pharmacokinetic analysis of the data revealed a monophasic serum clearance curve, which demonstrates slow elimination of bleomycin, being less than 500 ml/min and a half-time of 30 min.
  
  
  
  Slow monophasic elimination of bleomycin from serum in elderly patients implies on the longer therapeutic window, from 8 to up to 40 min or even longer post-bleomycin injection for electrochemotherapy. However, prolonged therapeutic bleomycin serum concentrations may also affect the possible adverse effects, such as lung fibrosis and extensive necrosis of tumors due to the uptake of toxic bleomycin concentrations into the tumors. This may imply on lowering of bleomycin dosage, in particular in the elderly patients.
authors.affiliation: Department of Otorhinolaryngology and Cervicofacial Surgery, University Medical Centre Ljubljana, Zaloska 2, 1000, Ljubljana, Slovenia.
authors.forename: Ales
authors.initials: A
authors.lastname: Groselj
authors.affiliation: Department of Pharmacology and Experimental Toxicology, Faculty of Medicine, University of Ljubljana, Korytkova 2, Ljubljana, Slovenia.
authors.forename: Mojca
authors.initials: M
authors.lastname: Krzan
authors.affiliation: Department of Environmental Sciences, Jozef Stefan Institute, Jamova 39, 1000, Ljubljana, Slovenia.
authors.forename: Tina
authors.initials: T
authors.lastname: Kosjek
authors.affiliation: Department of Experimental Oncology, Institute of Oncology Ljubljana, Zaloska 2, 1000, Ljubljana, Slovenia.
authors.forename: Masa
authors.initials: M
authors.lastname: Bosnjak
authors.affiliation: Department of Experimental Oncology, Institute of Oncology Ljubljana, Zaloska 2, 1000, Ljubljana, Slovenia. gsersa@onko-i.si.
authors.forename: Gregor
authors.initials: G
authors.lastname: Sersa
authors.affiliation: Department of Experimental Oncology, Institute of Oncology Ljubljana, Zaloska 2, 1000, Ljubljana, Slovenia. mcemazar@onko-i.si.|Faculty of Health Sciences, University of Primorska, Polje 42, 6310, Izola, Slovenia. mcemazar@onko-i.si.
authors.forename: Maja
authors.initials: M
authors.lastname: Cemazar
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D001761:Bleomycin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D053672:Electrochemotherapy / Q000379:methods*; D005260:Female; D006258:Head and Neck Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D011446:Prospective Studies; D066066:Response Evaluation Criteria in Solid Tumors; D012878:Skin Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000903:Antibiotics, Antineoplastic; D001761:Bleomycin
keywords: Bleomycin; Elderly patients; Electrochemotherapy; Head and neck tumors; Pharmacokinetics; Skin metastases