Pharmacokinetics of carboplatin at a dose of 750 mg m-2 divided over three consecutive days

Abstract

Summary Pharmacokinetics of the cisplatin analogue carboplatin were studied in patients with disseminated ovarian and testicular cancer. Carboplatin 750 mg m-2 divided over three consecutive days was given as part of an ablative combination regimen followed by autologous bone marrow transplantation. Platinum (Pt) in plasma, plasma ultrafiltrate and urine was determined up to 96 h after the last drug dose by atomic absorption spectrometry. Carboplatin was measured by high performance liquid chromatography. The curves of ultrafiltrated Pt and carboplatin decayed in a bio-exponential way with t1/2 a of respectively 65 and 70 min and t112 P of repectively 378 and 1014 min. The volumes of distribution (Vd,) were 18 and 25 1 m-2, respectively, and total body clearances (CITB) 79 and 65 ml min-m-2. Both curves overlapped when corrected for the Pt content of carboplatin. A diversion with the three-exponential curve of total Pt occurred between 3 and 6 h.

Carboplatin pharmacokinetics in patients receiving carboplatin and paclitaxel/docetaxel for advanced lung cancers: impact of age and renal function on area under the curve

“…The current study con®rms the previously described characteristics of the pharmacokinetics of carboplatin Huizing et al 1997;Trump et al 1987;Curt et al 1983;Harland et al 1984;van Hennik et al 1987;Newell et al 1993;Riccardi et al 1994;Desoize et al 1996;Shea et al 1989;Mulder et al 1990;van Warmerdam et al 1996b;Benezet et al 1997;Wright et al 1995;Olver et al 1995;van Warmerdam et al 1996a;Guillet et al 1997;Duull et al 1997;Okamoto et al 1998). Especially, the bi-phasic decay of plasma levels of ultra®ltrable platin and the relatively high variabilty of the parameters were found consistently in the current analyses as well as in prior ones.…”

“…However, the current data dier from previous reports in that a slightly longer terminal elimination half-life (13.6 h versus 1.4 to 6.3 h) and a higher value for total clearance (579 ml/min versus 79±222.3 ml/min) were observed. This might be due to the relatively small numbers of patients in most of the prior studies (between three and 19 patients Huizing et al 1997;Trump et al 1987;Curt et al 1983;Harland et al 1984;van Hennik et al 1987;Desoize et al 1996;Mulder et al 1990;van Warmerdam et al 1996b;Wright et al 1995;Olver et al 1995;van Warmerdam et al 1996a;Duull et al 1997) and also due to the limited number of samples taken from individual patients in some of these studies resulting in an inadequate calculation of the respective parameters.…”

Toxicity of High‐Dose Carboplatin: Ultrafiltered and Not Total Plasma Pharmacokinetics Is of Clinical Relevance

“…23 In contrast, terminal half-life of Pt uf (35 h) differed remarkably from literature (2-8 h). 24,25,27,28 Interestingly, the smallest values sometimes determined for conventional dosing correspond to our initial half-life. One explanation may be that due to smaller doses and concentrations, not only the quantification limit but also the length of the sampling period might be of relevance.…”

“…where C is the Pt concentration at time point t, T is the infusion duration, z is the number of compartments, C x is the coefficient, and λ x is the hybrid rate constant of each compartment. For patients with the optimized sampling schedule (group 2, patients [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29], an individual data analysis was performed. For patients 1 through 10 (group 1), the Bayesian approach (mean and variance of group 2 as initial values) was used due to the limited number of samples per patient in the elimination phase (see below).…”