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Comparison of different semi-mechanistic models for chemotherapy-related neutropenia: application to BI 2536 a Plk-1 inhibitor


, : Comparison of different semi-mechanistic models for chemotherapy-related neutropenia: application to BI 2536 a Plk-1 inhibitor. Cancer ChemoTherapy and Pharmacology 68(6): 1517-1527

The aim of this investigation was to compare the performance of a commonly used semi-mechanistic model for drug-related neutropenia with other semi-mechanistic models published in the literature. After their implementation in NONMEM VI, five semi-mechanistic models were assessed using the pharmacokinetic and absolute neutrophil count data obtained from 95 patients with non-small cell lung cancer receiving either 2 mg on day 1 or 5 or 6 mg on days 1, 2 and 3 of a 21-day treatment course with the new Plk-1 inhibitor BI 2536. The model performance was compared by means of predictive (visual and numerical) checks, precision in the parameter estimates and objective function-based measures. Details of model parameterization, model stability and run times are also provided. The time course of the drug plasma concentrations was described by a three compartment model with a first-order elimination rate. With respect to neutropenia, all models were successfully implemented in NONMEM and provided reasonable fits for the median (although not all models described all percentiles of the data well), and in general precise parameter estimates. In the current evaluation performed in a single drug, none of the models showed superior performance compared to the most commonly used model first described by Friberg et al. (J Clin Oncol 2:4713 4721, 22).

US$19.90

PMID: 21516508

DOI: 10.1007/s00280-011-1647-3


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Burgos-Flórez, F.J.; Gavilán-Alfonso, M.E.; Garzón-Alvarado, D.A., 2016: Flat bones and sutures formation in the human cranial vault during prenatal development and infancy: A computational model. The processes of flat bones growth, sutures formation and interdigitation in the human calvaria are controlled by a complex interaction between genetic, biochemical and environmental factors that regulate bone formation and resorption during prena...

Ast, S.; Nia, R.Moghadas.; Schönbeck, A.; Lastzka, N.; Steinlechner, J.; Eberle, T.; Mehmet, M.; Steinlechner, S.; Schnabel, R., 2011: High-efficiency frequency doubling of continuous-wave laser light. We report on the observation of high-efficiency frequency doubling of 1550 nm continuous-wave laser light in a nonlinear cavity containing a periodically poled potassium titanyl phosphate crystal (PPKTP). The fundamental field had a power of 1.1...

Thaler, H., 1949: Vitamin C content of milk preparatins for infants. This review is based mainly on a thesis by Heukamp (Univ., Munich, 1945). The dichlorophenol-indophenol titration is described as it was used by Heukamp for the determination of the vitamin C content of infant milk preparations in liquid, paste or...

Kimura, J.; Nakajima, Y.; Omura, T.; Tamura, M.; Ito, K.; Isai, H.; Nishikawa, M.; Takahashi, M.; Saiki, I.; Kusumoto, K., 1994: Warm ischemia impairs calcium metabolism in porcine grafted liver. Transplantation Proceedings 26(4): 2272-2273

Martz, M., 1986: A different approach to psychiatric benefits. Healthspan 3(10): 20-21

Nagata M.; Fugono R.; Sugimoto J., 1971: Effect of a low potassium medium on isolated guinea pig atria and interference of thiamine related compounds. Folia Pharmacol Jap 67(2): 5-6

Naji, A.; Sarabadani, J.; Dean, D.S.; Podgornik, R., 2012: Sample-to-sample torque fluctuations in a system of coaxial randomly charged surfaces. Polarizable randomly charged dielectric objects have been recently shown to exhibit long-range lateral and normal interaction forces even when they are effectively net-neutral. These forces stem from an interplay between the quenched statistics of...

Mäkelä, O.; Seppälä, I.J.; Pelkonen, J.; Kaartinen, M.; Cazenave, P.A.; Gefter, M.L., 1984: Crossing-over frequency in the Igh region of the mouse genome. An analysis of recombinations between strains C57BL and BALB/c at the Igh locus suggest that only strains B X D20 and B X D27 recombined in this region. This implies that the maps of Igh markers in strains C57BL, DBA/2 and BALB/c resemble one anot...

Eastham, R.D.; Cox, P.A., 1965: Screening Test For Urinary Amphetamine. British Medical Journal 1(5439): 924-925

Maeda, Y.; Nitta, K.; Arai, Y.; Yui, Y.; Shida, T.; Muraoka, T.; Iwahara, M., 1983: Time-frequency spectrum analysis of lung sounds in asthmatics. Nihon Kyobu Shikkan Gakkai Zasshi 21(7): 639-645