title: Prospective evaluation of pharmacokinetically guided dosing of carboplatin in Japanese patients with cancer.
abstract: The Calvert formula, that is, carboplatin dose (mg) = target area under the concentration versus time curve (AUC) × (glomerular filtration rate [GFR] + 25), has not been validated in Japanese subjects in whom the GFR was accurately measured. The purpose of this study is to evaluate the validity of this formula for Japanese patients with cancer and modify it for this population. The GFR was measured on the basis of inulin clearance, which is considered to reflect the accurate GFR. Inulin clearance was measured in 28 patients with cancer. The adjusted 24-h creatinine clearance (24-h Ccr) was unbiased (mean prediction error [MPE] ± SE = -2.3 ± 4.5%) and acceptably precise (root mean squared error = 23.7%) for GFR assessment. The pharmacokinetics of carboplatin were analyzed in 21 patients with a GFR of 17.2-91.4 mL/min. The original Calvert formula overestimated carboplatin clearance, resulting in an MPE of 14.3%. When we revised the Calvert formula for Japanese patients by substituting a non-renal clearance of 15 for 25, that is, dose = target AUC × (GFR + 15), the MPE decreased to -0.1% (P < 0.001). We conclude that the adjusted 24-h Ccr is acceptably precise for GFR assessment, and the non-renal clearance of carboplatin is suggested to be lower in Japanese patients with cancer than in their Western counterparts.
authors.affiliation: Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Shimokata
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ando
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Yasuda
authors.forename: Akinobu
authors.initials: A
authors.lastname: Hamada
authors.forename: Kenji
authors.initials: K
authors.lastname: Kawada
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Saito
authors.forename: Seiichi
authors.initials: S
authors.lastname: Matsuo
authors.forename: Masashi
authors.initials: M
authors.lastname: Kondo
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Imaizumi
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Hasegawa
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D044466:Asian People; D016190:Carboplatin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D016190:Carboplatin