Abstract
A limited sampling model for the estimation of the carboplatin area under the concentration versus time curve (AUC), as developed by Sørensen et al., was validated prospectively for the use in a high-dose combination chemotherapy schedule. The model allows an estimation of the AUC on the basis of only one timed plasma drug concentration, sampled at exactly 2.75 h after a 1-h carboplatin infusion. Pharmacokinetic curves were obtained from nine patients receiving carboplatin (400 mg/m2 per day) combined with cyclophosphamide (1500 mg/m2 per day), thiotepa (120 mg/m2 per day), and mesna (3 g/day) for 4 consecutive days. Peripheral blood stem-cell transplantation (PBSCT) was performed 3 days later to restore hematopoiesis. Using this combination of high doses, the model proved to be unbiased (MPE −3.40%; SE, 1.22%) and highly precise [root mean squared prediction error (RMSE), 5.15%; SE, 0.17%] for estimation of the AUC during 4 consecutive days. The validated limited sampling model provides a starting point for future pharmacokinetic studies in a larger population of patients, which might lead to more insight into the relationships with the pharmacodynamic outcome of carboplatin and may help in achieving more rational dosing of patients on the basis of an AUC determination.
References
Chiou WL (1989) The phenomenon and rationale of marked dependence of drug concentration on blood sampling site; implications in pharmacokinetics, pharmacodynamics, toxicology and therapeutics. Clin Pharmacokinet 17: 175
Horwich A, Dearnaley DP, Nicholls J, Jay G, Mason M, Harland S, Peckham MJ, Hendrey WF (1991) Effectiveness of carboplatin, etoposide, and bleomycin combination chemotherapy in goodprognosis metastatic testicular nonseminomatous germ cell tumors. J Clin Oncol 9: 62
Jodrell DI, Egorin MJ, Canetta RM, Langenberg P, Goldbloom EP, Burroughs JN, Goodlow JL, Tan S, Wiltshaw E (1992) Relationships between carboplatin exposure and tumor response and toxicity in patients with ovarian cancer. J Clin Oncol 10: 520
Rodenhuis S, Baars JW, Schornagel JH, Vlasveld LT, Mandjes I, Pinedo HM, Richel DJ (1992) Feasibility and toxicity study of a high-dose chemotherapy regimen for autotransplantation incorporating carboplatin, cyclophosphamide and thiotepa. Ann Oncol 3: 855
Sørensen BT, Strömgren A, Jakobsen P, Jakobsen A (1993) A limited sampling method for estimation of the carboplatin area under the curve. Cancer Chemother Pharmacol 31: 324
Van Warmerdam LJC, Ten Bokkel Huinink WW, Maes RAA, Beijnen JH (1994) Limited sampling models for anticancer agents. J Cancer Res Clin Oncol 120: 427
Wagstaff AJ, Ward A, Benfield P, Heel RC (1989) Carboplatin, a preliminary review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy in the treatment of cancer. Drugs 37: 162
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van Warmerdam, L.J.C., Rodenhuis, S., van Tellingen, O. et al. Validation of a limited sampling model for carboplatin in a high-dose chemotherapy combination. Cancer Chemother. Pharmacol. 35, 179–181 (1994). https://doi.org/10.1007/BF00686644
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DOI: https://doi.org/10.1007/BF00686644