title: A universal formula based on cystatin C to perform individual dosing of carboplatin in normal weight, underweight, and obese patients.
abstract: OBJECTIVE
  It has recently been shown that it is possible to improve the prediction of carboplatin clearance by adding plasma cystatin C level (cysC), an endogenous marker of glomerular filtration rate, to the other patient characteristics routinely used for carboplatin individual dosing, namely serum creatinine (Scr), actual body weight (ABW), age, and sex. This multicenter pharmacokinetic study was done to evaluate prospectively the benefit of using cysC for carboplatin individual dosing.
  
  
  METHODS
  The 357 patients included in the study were receiving carboplatin as part of established protocols. A population pharmacokinetic analysis was done using NONMEM program. Seven covariates studied were as follows: Scr, cysC, age, sex, ABW, ideal body weight, and lean body mass.
  
  
  RESULTS
  The best covariate equation was as follows: carboplatin clearance (mL/min) = 117.8. (Scr/75)(-0.450). (cysC/1,00)(-0.385). (ABW/65)(+0.504). (age/56)(-0.366). 0.847(sex), with Scr in micromol/L, cysC in mg/L, ABW in kilograms, age in years, and sex = 0 for male. Using an alternative weight descriptor (ideal body weight or lean body mass) did not improve the prediction. This final covariate model was validated by bootstrap analysis. The bias (mean percentage error) and imprecision (mean absolute percentage error) were +1% and 15%, respectively, on the total population, and were of a similar magnitude in each of the three subgroups of patients defined according to their body mass index.
  
  
  CONCLUSIONS
  For the first time, a unique formula is proposed for carboplatin individual dosing to patients, which is shown to be equally valid for underweight, normal weight, and obese patients.
authors.affiliation: Institut Claudius-Regaud and EA3035 University of Toulouse, Toulouse, France.
authors.forename: Antonin
authors.initials: A
authors.lastname: Schmitt
authors.forename: Laurence
authors.initials: L
authors.lastname: Gladieff
authors.forename: Amélie
authors.initials: A
authors.lastname: Lansiaux
authors.forename: Christine
authors.initials: C
authors.lastname: Bobin-Dubigeon
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Etienne-Grimaldi
authors.forename: Michèle
authors.initials: M
authors.lastname: Boisdron-Celle
authors.forename: Françoise
authors.initials: F
authors.lastname: Serre-Debauvais
authors.forename: Frédéric
authors.initials: F
authors.lastname: Pinguet
authors.forename: Anne
authors.initials: A
authors.lastname: Floquet
authors.forename: Eliane
authors.initials: E
authors.lastname: Billaud
authors.forename: Chantal
authors.initials: C
authors.lastname: Le Guellec
authors.forename: Nicolas
authors.initials: N
authors.lastname: Penel
authors.forename: Mario
authors.initials: M
authors.lastname: Campone
authors.forename: Rémy
authors.initials: R
authors.lastname: Largillier
authors.forename: Olivier
authors.initials: O
authors.lastname: Capitain
authors.forename: Michel
authors.initials: M
authors.lastname: Fabbro
authors.forename: Nadine
authors.initials: N
authors.lastname: Houede
authors.forename: Jacques
authors.initials: J
authors.lastname: Medioni
authors.forename: Philippe
authors.initials: P
authors.lastname: Bougnoux
authors.forename: Isabelle
authors.initials: I
authors.lastname: Lochon
authors.forename: Etienne
authors.initials: E
authors.lastname: Chatelut
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D000704:Analysis of Variance; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D015992:Body Mass Index; D001835:Body Weight / Q000502:physiology; D016190:Carboplatin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D055316:Cystatin C / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007118:Immunoassay / Q000379:methods; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D009765:Obesity / Q000503:physiopathology; D011446:Prospective Studies; D015203:Reproducibility of Results; D014018:Tissue Distribution; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D055316:Cystatin C; D016190:Carboplatin