排序方式: 共有23条查询结果,搜索用时 15 毫秒
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Amit Garg Angelica Quartino Jing Li Jin Jin D. Russell Wada Hanbin Li Javier Cortés Virginia McNally Graham Ross Jennifer Visich Bert Lum 《Cancer chemotherapy and pharmacology》2014,74(4):819-829
Purpose
To characterize the population pharmacokinetics (PK) of pertuzumab across clinical trials in a variety of solid tumors, evaluate the potential impact of patient characteristics on PK, and confirm the appropriateness of the fixed (non-weight-based) dose.Methods
Pertuzumab concentration data collected following intravenous administration during eleven phase I/II studies and the pivotal phase III trial CLEOPATRA were analyzed using nonlinear mixed-effects modeling. The potential impact of patient and laboratory characteristics and HER2 target-related variables on pertuzumab PK were investigated in a covariate analysis. The final model was used to confirm selection of fixed, non-weight-based dosing of pertuzumab, and to compare pertuzumab PK in CLEOPATRA with the other studies.Results
The analysis included 4,525 serum concentration measurements from 481 patients with solid tumors. Pertuzumab PK in the 2–25 mg/kg dose range was described by a two-compartment linear model with first-order elimination. The elimination clearance and central compartment volume were 0.235 L/day, and 3.11 L, respectively, and the terminal elimination half-life was 18.0 days. Baseline serum albumin and lean body weight had statistically significant effects on pertuzumab clearance; however, simulations showed that the magnitude of their effects on pertuzumab exposure was minimal compared with overall variability and was not clinically relevant. Thus, variations in these factors do not require dose adjustments.Conclusions
The fixed, non-weight-based dosing of pertuzumab, 840 mg loading dose followed by a 420 mg maintenance dose every 3 weeks, in patients with the solid tumors in this analysis is well supported by the population pharmacokinetic modeling and simulation results. 相似文献3.
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Kawakatsu Sonoko Zhu Rui Zhang Wenhui Tang Meina T. Lu Tong Quartino Angelica L. Kågedal Matts 《Journal of pharmacokinetics and pharmacodynamics》2022,49(2):179-190
Journal of Pharmacokinetics and Pharmacodynamics - Clinical trials in patients with ulcerative colitis (UC) face the challenge of high and variable placebo response rates. The Mayo Clinical Score... 相似文献
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Purpose To improve the predictive capacity of a semi-mechanistic myelosuppression model for neutrophils as the model have shown to
over-predict the nadir of neutrophils and, secondly, to develop a model describing the time-course of leukocytes and neutrophils
simultaneously. Experimental Design The study included 601 cancer patients treated with a 1 h infusion of docetaxel in monotherapy. A total of 3,549 pairwise
observations of leukocytes and neutrophils from one treatment cycle were analyzed simultaneously in NONMEM. Results A basic model was developed consisting of a neutrophil and a non-neutrophil model, each with the same structure as the semi-mechanistic
myelosuppression model. The leukocytes were modeled as the sum of the predicted neutrophils and non-neutrophils. The model
described the time-course of the leukocytes well, but was not able to capture the nadir of the neutrophils. Hence the model
was further refined and the included modifications (p < 0.001) in the final model are a sigmoid Emax functions for the drug effect, feedback functions on the cell maturation time
in bone-marrow and an optimized number of transit compartments for each of the two cell types. Conclusions A joint semi-mechanistic myelosuppression model describing the time-course of leukocytes and neutrophils following docetaxel
administration was developed. The data supported a more complex model compared to the previous model developed by Friberg
et al. (2002), and increased the model’s capacity to accurately describe the time-course of neutrophils following docetaxel
therapy. The combined model also illustrates the differences between the cell types and allows prediction of neutrophil counts
from leukocyte measurements. 相似文献
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Bogason A Quartino AL Lafolie P Masquelier M Karlsson MO Paul C Gruber A Vitols S 《British journal of clinical pharmacology》2011,71(4):514-521
AIMS
It has been shown that the cellular uptake and cytotoxicity of anthracyclines decrease with increasing cell density in vitro, an event termed ‘the inocculum effect’. It is not known whether such an effect occurs in vivo. In this study the relationships between white blood cell (WBC) count, plasma and cellular concentrations of daunorubicin (DNR) in patients with acute myeloid leukaemia were investigated.METHODS
Plasma and mononuclear blood cells were isolated from peripheral blood from 40 patients with acute myeloid leukaemia at end of infusion (time 1 h), 5 and 24 h following the first DNR infusion. DNR concentrations were determined by high-pressure liquid chromatography and related to the WBC count at diagnosis. A population pharmacokinetic model was used to estimate the correlations between baseline WBC count, volume of distribution and clearance of DNR.RESULTS
A clear but weak inverse relationship between the baseline WBC count and plasma concentrations of DNR (r2 = 0.11, P < 0.05) at time 1 was found. Furthermore, a clear relationship between baseline WBC count and DNR central volume of distribution using population pharmacokinetic modelling (dOFV 4.77, P < 0.05) was also noted. Analysis of plasma DNR and the metabolite daunorubicinol (DOL) concentrations in patients with a high WBC count support that the low DNR/DOL concentrations are due a distribution effect.CONCLUSION
This study shows that the leukaemic cell burden influences the plasma concentrations of anthracyclines. Further studies are needed to explore if patients with high a WBC count may require higher doses of anthracyclines. 相似文献7.
A Rasore Quartino 《Pathologica》1967,59(873):145-151
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