The disposition of carboplatin in ovarian cancer patients

✍ Scribed by Robert C. Gaver; Nicoletta Colombo; Michael D. Green; Alice M. George; George Deeb; Alan D. Morris; Renzo M. Canetta; James L. Speyer; Raymond H. Farmen; Franco M. Muggia

• Publisher: Springer
• Year: 1988
• Tongue: English
• Weight: 908 KB
• Volume: 22
• Category: Article
• ISSN: 0344-5704
• DOI: 10.1007/bf00273422

✦ Synopsis

Carboplatin was given as a 30-min infusion to 11 ovarian cancer patients at doses of 170-500 mg/m 2. The ages, weights, and creatinine clearances (Clef) ranged from 44 to 75 years, from 44 to 74 kg, and from 32 to 101 ml/ min, respectively. Plasma, plasma ultrafiltrate (PU), and urine samples were obtained at appropriate times for 96 h and were analyzed for platinum. The PU and urine were also analyzed for the parent compound by HPLC. In patients with a Clcr of about 60 ml/min or greater, carboplatin decayed biexponentially with a mean t,n~ of 1.6 h and a t,/2~ of 3.0 h. The mean (_ SD) residence time, total body clearance, and apparent volume of distribution were 3.5__+0.4h, 4.4_-L-0.851/h, and 16___3 1, respectively. Cma x and AUCinf values increased linearly with dose, and the latter values correlated better with the dose in mg than in mg/m 2. No significant quantities of free, ultrafilterable, platinum-containing species other than the parent compound were found in plasma, but platinum from carboplatin became protein-bound and was slowly eliminated with a minimal t,/2 of 5 days. The major route of elimination was excretion via the kidneys. Patients with a Clcr of 60 ml/min or greater excreted 70% of the dose as the parent compound in the urine, with most of this occurring within 12-16 h. All of the platinum in 24-h urine was carboplatin, and only 2%-3% of the dosed platinum was excreted from 48 to 96 h. Patients with a Clor of less than about 60 ml/ min exhibited dose-disproportional increases in AUCin f and MRT values. The latter were inversely related to Cl¢r (r = -0.98). Over a dose range of 300-500 mg/m 2, carboplatin exhibited linear, dose-independent pharmacokinetics in patients with a Clcr of about 60 ml/min or greater, but dose reductions are necessary for patients with mild renal failure.