and methadone, 219 Pegylation G-CSF, 151

increasing hydrodynamic volume through,

148-150 PEG-asparaginase, 150 PEGylated interferon, 151 site-specific, 150 Pepsin, 200 Peptide fusions, 137

Peptide YY3-36 (PYY), 192 Permeation enhancers role of, IN delivery and, 179 PET. See Positron emission tomography (PET) PFS. See Progression free survival (PFS) P-glycoprotein (P-gp)

effect of IFN-a on, in vivo, 210-211 P-gp. See P-glycoprotein (P-gp) PGs. See Proteoglycans (PGs) Pgx. See Pharmacogenomics (Pgx) Pharmacodynamics (PD), 3, 173 antibody binding and, 30 potency and, 30-36 drug interaction heparin and abciximab, 220 heparin and aspirin on YM337, 220 Peg-IFN-a2b and methadone, 219 prednisolone and IL-10, 219 reviparin and abciximab, 220 xemilofiban and abciximab, 219-220 effects of IN insulin formulations, 182 markers, mechanism- and disease-

associated, 235 systemic versus portal circulation, 195 Pharmacogenomics (Pgx) as business strategy, 242 definition of, 225 in drug development identify targets, 226-227 patient selection and stratification, 227 strategy overview, 226 effect of patient variability on exposure. See Patient variability on response. See Patient variability gene expression and, 231 Her2/neu expression and, 230 immunogenicity predictions computational approaches to, 239-240 development of anti-drug antibody responses, 237-238 MHC genetics and, 238-239 marker, 230 promise of, 225-226 strategies in clinical care, 241-242 hypothesis-based approaches, 228-229 non-hypothesis-based approaches, 229-230 statistical considerations, 230-231 stratified medicine and targeted therapies, intersection between, 240-241 Pharmacokinetics (PK), 3, 173 ADC, in vitro plasma stability related to, 42 antibody. See Antibody pharmacokinetics (Ab PK)

[Pharmacokinetics (PK)] AUC versus peak concentration, 195-196 drug interaction, 210 effects of IN insulin formulations, 182 and identification of Pgx markers, 234 systemic versus portal circulation, 195 Physiologically based pharmacokinetic

(PBPK) modeling tools, 15-16 Pigment epithelium-derived factor (PEDF), 169 Pinocytosis, 210 Pittsburgh mixture, 213 PK. See Pharmacokinetics (PK) PKC. See Protein kinase C (PKC) Platelet-derived growth factor (PDGF), 54, 110

PLGA. See Polylactic acid-glycolic acid (PLGA)

Polyethylene glycol (PEG), 131, 148

maleimide-derivatized, 148 Polylactic acid-glycolic acid (PLGA), 115, 169 Polymer alternative, 152-153 conjugation, future directions in, 151 Polymorphisms FCGRT, 233 VNTR, 233 Polymorphonuclear leukocytes, 109 Positron emission tomography (PET), 21 Potency antibody PD and, 30-36 defined, 30 Prednisolone and IL-10, 219

pharmacokinetic parameters of, 215 Prednisone, 215

Progression free survival (PFS), 227

Prostate stem cell antigen (PSCA), 39

Protein engineering, 129

Protein kinase C (PKC), 62

Proteoglycans (PGs), 83

PSCA. See Prostate stem cell antigen (PSCA)

PSMB8 genetic variant, 235


CD11a as target for, 22, 33 PTH1-34. See Human parathyroid hormone

1-34 (PTH1-34) Pulsatile insulin, 195 PYY. See Peptide YY3-36 (PYY)

Radioimmunoconjugates, 18, 20 Radioimmunoscintigraphy, 20-21 Radionuclides, 20-21 Ranibizumab (Lucentis®, anti-VEGF-A), 36, 166

Raptiva®. See Efalizumab RCD4. See Recombinant CD4 ectodomain (rCD4)

Receptor-mediated endocytosis (RME), 209-210

Recombinant CD4 ectodomain (rCD4), 134 Recombinant hematopoietic cytokines, 2-3 Recombinant human interferon-a (rhIFN-a), 211, 212

Recombinant tumor necrosis factor (rTNF)

effect of, on CYP450 system, 216 Renal excretion, 209

RES. See Reticuloendothelial system (RES) Resolution, tissue defined, 107-108 Rete pegs, defined, 84 Reticulocytes, 7

Reticuloendothelial system (RES), 36 Reviparin and abciximab, 220 RGD. See Arginine-glycine-aspartate (RGD) Rheumatoid arthritis

CD20, as target for, 33-34 RhIFN-a. See Recombinant human interferon-a (rhIFN-a) RME. See Receptor-mediated endocytosis (RME)

RTNF. See Recombinant tumor necrosis factor (rTNF)

Salmon calcitonin (sCT), 179, 192

oral, 200-201 SC. See Subcutaneous (SC) injection SCF. See Stem cell factor (SCF) SCF gene, 4

ScFv. See Single-chain variable fragment (scFv)

SC injection. See Subcutaneous (SC) injection SC injection site, 81 architecture of, 82-83 components and properties, 83-84 defined, 82-83

interstitial fluid composition, 85 intramuscular and intradermal injections, comparison of, 98 nerves and vessels of, 84-85 proteins and peptides, modifications of, 90-91 biological stresses, 94 chemical stresses, 93-94 physical stresses, 92-93 proteins and peptides uptake from absorption, mechanisms of, 96-97 dose volume limitations, 97-98

[SC injection site proteins and peptides uptake from] nonspecific vs. specific, 95 tissue damage due to needle introduction, 95-96 tissue responses fluid-induced distention, impact of, 88-89 to injected protein/peptide, 86-88 interstitial fluid composition and return to steady-state conditions, dilution of, 89-90

needle penetration, events stimulated by, 85-86 Sclera, 165

SCT. See Salmon calcitonin (sCT) SEAP. See Secreted alkaline phosphatase (SEAP)

SEC. See Size-exclusion chromatography (SEC)

Secreted alkaline phosphatase (SEAP), 169

Serine proteases, 197

Serum albumin, 131. See also Albumins properties of, 139-141, 142 SGN-40, 34

Single-chain variable fragment (scFv), of ABs, 20 Single-domain antibodies (dAbs), 146 Single-nucleotide polymorphism (SNP), 226-227

Single-photon emission computed tomography (SPECT), 21 Size-exclusion chromatography (SEC), 148 Skin, structure of, 82-83 Small molecular weight drugs (SMD), 15-16

SMD. See Small molecular weight drugs (SMD)

SNP. See Single-nucleotide polymorphism (SNP)

SOCS-1. See Suppressor of cytokine signaling

1 (SOCS-1) SOD. See Superoxide dismutase (SOD) SOWS. See Subjective opiate withdrawal scale (SOWS)

SPECT. See Single-photon emission computed tomography (SPECT) Spleen colony-forming units (CFU-S), 1 Stem cell factor (SCF), 2, 3-4. See also Stemgen granulocyte signaling in, 4 PK parameters in human, 4 Stemgen, 3-4. See also Stem cell factor

(SCF) Stratification, 227

Subcutaneous (SC) injection, 184, 2CS, 2C7 marketing of protein and peptide therapeutics and, 8C site. See SC injection site Subjective opiate withdrawal scale

(SOWS), 219 Superoxide dismutase (SOD), 141 Suppressor of cytokine signaling 1 (SOCS-1), 2S1

Target-mediated drug disposition modeling

T-cell receptor (TCR), 238

TCR. See T-cell receptor (TCR)

TDDM. See Target-mediated drug disposition modeling (TDDM) TEER. See Transepithelial resistance (TEER) TER. See Transepithelial electrical resistance (TER)


11-tetraacetic acid (64Cu-TETA), 28 TGF-ß. See Transforming growth factor ß

(TGF-ß) Thrombocytopenia, 8, 138 Thrombopoietin (TPO), 3, 8-9 Thrombus. See Blood clot formation Tight junction (TJ), 173 Tissue/material responses defined, 106 early transient blood-material interactions and, 108 granulation tissue, 116 inflammation. See Inflammation injury and acute responses to, 107-110 late persistent fibrous encapsulation, 121-122 foreign body reaction, 116-121 implanted drug delivery systems to modulate, 122-123 Tissue plasminogen activators, 207-208 TJ. See Tight junction (TJ) TK. See Toxicokinetics (TK) TNF. See Tumor necrosis factor (TNF) TNF-a. See Tumor necrosis factor (TNF-a) Toxicokinetics (TK), 203 TPO. See Thrombopoietin (TPO) Transepithelial electrical resistance (TER), 182 Transepithelial resistance (TEER), 180 Transforming growth factor ß (TGF-ß), 54, 110 Transscleral protein delivery of, 168-169 Trastuzumab, 34, 232

Tropoelastins, 84 TRX1, 30

Tumor necrosis factor (TNF), 235 effect of recombinant on CYP450 system, 216 Tumor necrosis factor (TNF-a), 35

Variable number of tandem repeats (VNTR)

polymorphism, 233 Vascular endothelial growth factor (VEGF), 35-36, 54, 56-57, 94, 163 fibronectin interactions with, 62 heparin-binding, 58-59 VEGF. See Vascular endothelial growth factor

(VEGF) VEGF-A expression, 56

Virtual matrices, 239 Vitreous humor, 166

drug elimination from, 167 VNTR polymorphism. See Variable number of tandem repeats (VNTR) polymorphism Vroman effect, 108

Warfari etanercept and, 217 Wound healing, 1100-111

Xemilofiban, 219-220 Xenobiotics, 163 Xolair®. See Omalizumab

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