title: PAC fixed dose: pharmacokinetics of a 1-hour paclitaxel infusion and comparison to BSA-normalized drug dosing.
abstract: BACKGROUND
  The aim of this study was to determine the pharmacokinetics (PKs) of a 175-mg fixed dose of paclitaxel (PAC) after a 1-h infusion in cancer patients and to compare them with the PK parameters from a study with a dose normalized to the body surface area (BSA) (100 mg/m2).
  
  
  METHODS
  PAC PKs were studied during the first course of therapy in 13 patients. A fixed dose of 175 mg PAC was administered weekly by a 1-h infusion to patients with advanced cancer. Total PAC in serum was quantified by high-performance liquid chromatography (HPLC). PK parameters were calculated by non-compartmental and model-dependent methods.
  
  
  RESULTS
  The mean BSA of 12 patients (1 patient excluded from all analyses because of prolonged infusion duration) was 1.79 m2 (coefficient of variation (CV) 7.8%), the mean dose referred to the individual BSAs was 98.3 mg/m2 (CV 8.3%). The mean area under the curve (AUC) was 6,193 ng/ml x h (CV 46%), the mean plasma clearance (Clp) was 19.7 l/h/m2 (CV 45%), and the volume of distribution at steady state (Vss) was 121.6 l/m2 (CV 52%). The mean residence time (MRT) was 7.6 h (CV 46%), the mean distribution half-life (t1/2 alpha) of PAC(tot) was 0.4 h (CV 62%), and the elimination half-life (t1/2 beta) 10.0 h (CV 42%). Maximum plasma concentration Cmax was 3,161 ng/ml (CV 36%). The mean time above 0.05 microM (42.7 ng/ml) was 19.7 h, and the mean time above 0.1 microM (85.4 ng/ml) was 10.6 h.
  
  
  CONCLUSIONS
  In this study, a fixed dose of PAC of 175 mg corresponds to a mean BSA-normalized dose of 98.3 mg/m2 (range 88.8-117.4 mg/m2). A higher variability of PK parameters was observed compared to previously published results of a PK study with BSA-normalized dosing of 100 mg/m2. However, the AUC and the time above threshold concentrations did not depend on the dose. Therefore, a fixed dose of 175 mg weekly could be an option for palliative treatment with PAC and may offer a simple but effective schedule for PAC treatment.
authors.affiliation: Department of Medical Oncology, Tumor Biology Center at the Albert-Ludwigs-University, Germany. mross@tumorbio.uni-freiburg.de
authors.forename: Klaus
authors.initials: K
authors.lastname: Mross
authors.forename: Norbert
authors.initials: N
authors.lastname: Holländer
authors.forename: Annette
authors.initials: A
authors.lastname: Frost
authors.forename: Clemens
authors.initials: C
authors.lastname: Unger
authors.forename: Vittorio
authors.initials: V
authors.lastname: Ziroli
authors.forename: Ulrich
authors.initials: U
authors.lastname: Massing
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D001830:Body Surface Area; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood* / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage* / Q000493:pharmacokinetics*
chemical_list: D000970:Antineoplastic Agents; D017239:Paclitaxel