BEVACIZUMAB EFFECT ON TOPOTECAN PHARMACOKINETICS ...

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Table 5. Population PK parameters of TPT estimated after SDBT Groups # T 1D BT 3D BT 7D BT Parameters Mean SD IIV Mean SD IIV Mean SD IIV Mean SD IIV Ke (1/h) 0.448 0.120 26.7 1.51 0.760 50.3 1.07 0.819 76.6 1.06 0.804 76.0 Vc (L/m 2 ) 14.1 3.71 26.2 12.7 6.66 52.4 13.7 9.33 68.2 12.6 6.93 54.8 Kcp (1/h) 0.627 0.448 71.4 1.59 1.57 99.2 1.32 1.33 100 0.604 0.700 116 Kpc (1/h) 0.588 0.0600 10.2 0.344 0.0987 28.6 0.791 0.631 79.7 0.667 0.0600 9.00 Kct (1/h) 2.11 0.395 18.7 1.48 0.288 19.5 1.83 0.706 38.6 1.42 0.194 13.6 Kte (1/h) 4.61 1.04 22.5 16.3 7.07 43.4 6.03 3.56 59.1 6.45 0.500 7.74 Vt (L/m 2 ) 2.12 0.239 11.3 0.307 0.173 56.4 1.78 1.36 76.6 1.50 0.399 26.6 MLEM program was used in this population modeling for each individual group. Mean and SD refer to population mean and population standard deviation; IIV refers to inter-individual variability as of %CV. 37
Table 6. Population PK parameters of TPT estimated after MDBT Groups # mT 1D mBT 3D mBT 7D mBT Parameters Mean SD IIV Mean SD IIV Mean SD IIV Mean SD IIV% Ke (1/h) 0.825 0.505 61.2 0.371 0.323 87.0 0.284 0.211 74.4 0.343 0.392 114 Vc (L/m 2 ) 9.61 2.22 23.1 8.81 2.24 25.5 11.2 5.01 44.6 10.8 7.97 73.7 Kcp (1/h) 1.35 1.61 119 4.93 1.30 26.3 4.06 1.43 35.3 1.88 2.82 150 Kpc (1/h) 0.795 0.538 67.7 0.966 0.471 48.8 1.14 0.891 78.1 0.602 0.383 63.6 Kct (1/h) 1.93 0.532 27.6 1.68 0.630 37.4 2.10 0.842 40.2 1.66 0.995 60.0 Kte (1/h) 15.8 10.1 63.9 11.3 8.54 75.4 15.3 18.9 124 14.0 10.7 76.2 Vt (L/m 2 ) 0.580 0.467 80.5 0.611 0.549 89.8 0.791 1.13 143 0.501 0.424 84.6 MLEM program was used in this population modeling for each group. Mean and SD refer to population mean and population standard deviation; IIV refers to inter-individual variability as of %CV 38
Page 1 and 2: BEVACIZUMAB EFFECT ON TOPOTECAN PHA
Page 3 and 4: ACKNOWLEDGEMENTS I would like to th
Page 5 and 6: overall effect of BEV on TPT pharma
Page 7 and 8: 2.3.1 The effect of BEV on the phar
Page 9 and 10: LIST OF FIGURES Figure 1. TPT effic
Page 11 and 12: SDBT Single dose of bevacizumab tre
Page 13 and 14: hypertension and the pathologic ext
Page 15 and 16: 1.1.3 Strategies to improve drug pe
Page 17 and 18: 1.2.2 Role of vascular endothelial
Page 19 and 20: enhanced the tumor response to conv
Page 21 and 22: non-favorable sites [109]. So devel
Page 23 and 24: low sensitivity. Additionally, it r
Page 25 and 26: tumor distribution of TMZ in V+ SC
Page 27 and 28: over-pruned microvessel [146, 147].
Page 29 and 30: 1.7 Summary Although the overall su
Page 31 and 32: CHAPTER 2. THE EFFECT OF BEVACIZUMA
Page 33 and 34: 2.2.4 Tumor model and treatment Ort
Page 35 and 36: Table 1. (SDBT) TPT penetration stu
Page 37 and 38: Figure 2. TPT penetration plus effi
Page 39 and 40: Figure 3. A pharmacokinetic model f
Page 41 and 42: 2.2.10 Statistical analyses For eac
Page 43 and 44: Figure 6. Representative plasma and
Page 45 and 46: Figure 7. The effect of BEV on the
Page 47: Figure 8. The effect of BEV on the
Page 51 and 52: variability for Kte decreased from
Page 53 and 54: Figure 11. The effect of different
Page 55 and 56: efflux transporters. TPT is a campt
Page 57 and 58: Furthermore, although the volume of
Page 59 and 60: 19. Sleeman, J., A. Schmid, and W.
Page 61 and 62: 56. ElBayoumi, T.A. and V.P. Torchi
Page 63 and 64: 91. Ma, J. and D.J. Waxman, Combina
Page 65 and 66: 125. Hao, M., et al., Pharmacokinet
Page 67 and 68: 154. Dickson, P.V., et al., Bevaciz
Page 69 and 70: 188. Tian, Q., et al., Topotecan is

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