title: Evaluation of a formula for individual dosage of nedaplatin based on renal function.
abstract: OBJECTIVE
  Nedaplatin (NDP), a platinum derivative, has been developed to reduce nephrotoxicity and gastrointestinal toxicity of cisplatin. The pharmacokinetic profile of NDP is similar to that of carboplatin (CBDCA). The optimal dosing for CBDCA is determined by the area under the curve (AUC) using Calvert's formula. However, the administration dose of nedaplatin (NDP) is determined based on the body surface area in clinical treatment. Ishibashi et al. reported a formula for predicting NDP clearance based on renal function like Calvert's formula for CBDCA. We conducted the present study to evaluate the Ishibashi's formula.
  
  
  METHODS
  A total of 22 patients with cervical or ovarian cancer, who underwent chemotherapy consisting of NDP and irinotecan (CPT-11), were examined in this study. Blood samples were collected at 0, 1, 2, 4, and 6 h after the end of infusion of NDP (48-80 mg/m(2)), and free platinum concentrations were measured. Observed AUCs were compared with predicted AUCs, which were calculated by the Ishibashi's formula. In addition, the relative reduction in platelets (PLTs) was assessed as a parameter of adverse effects.
  
  
  RESULTS
  The observed AUC of NDP ranged from 4 to 14 (μg h(-1) ml(-1)) with large variation. The predicted AUC based on renal function was correlated with the observed AUC. There was a relationship between observed AUC and the decrease in PLTs.
  
  
  CONCLUSIONS
  Ishibashi's formula would be predictable and useful for estimating the individual dose of NDP.
authors.affiliation: Department of Obstetrics and Gynecology, Tottori University, 36-1, Nishi-cho, Yonago City, Tottori, 683 8504, Japan. sshinya@med.tottori-u.ac.jp
authors.forename: Shinya
authors.initials: S
authors.lastname: Sato
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Fujiwara
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Oishi
authors.forename: Muneaki
authors.initials: M
authors.lastname: Shimada
authors.forename: Shizuo
authors.initials: S
authors.lastname: Machida
authors.forename: Yuji
authors.initials: Y
authors.lastname: Takei
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Itamochi
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Suzuki
authors.forename: Junzo
authors.initials: J
authors.lastname: Kigawa
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D019540:Area Under Curve; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects; D005260:Female; D006801:Humans; D007668:Kidney / Q000187:drug effects*; D007677:Kidney Function Tests; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008962:Models, Theoretical; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D010051:Ovarian Neoplasms / Q000097:blood / Q000188:drug therapy*; D010976:Platelet Count; D057285:Precision Medicine; D011237:Predictive Value of Tests; D002583:Uterine Cervical Neoplasms / Q000097:blood / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; C053989:nedaplatin