Pharmacokinetics, Lymph Node Uptake, and Mechanistic PK Model of Near-Infrared Dye-Labeled Bevacizumab After IV and SC Administration in Mice

Wu, Fang; Tamhane, Mitalee; Morris, Marilyn E.

doi:10.1208/s12248-012-9342-9

Cited by 31 publications

(27 citation statements)

References 28 publications

(32 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Comparable plasma concentration profiles for up to 24 hours measured by fluorescence and ELISA have been observed for bevacizumab with a high dye/protein labeling ratio (3.5) (Wu et al, 2012). Another study concluded that IRDye800 in a low dye/protein labeling ratio does not significantly alter the pharmacokinetics of cetuximab, which has a relatively short half-life at ASPET Journals on May 9, 2018 dmd.aspetjournals.org (2.5 days) (Zinn et al, 2015).…”

Section: Discussionmentioning

confidence: 93%

Biodistribution of Etanercept to Tissues and Sites of Inflammation in Arthritic Rats

Chen¹,

DuBois²,

Almon³

et al. 2015

Drug Metab Dispos

View full text Add to dashboard Cite

Many monoclonal antibodies (mAbs) and other protein drugs have targets usually residing within tissues, making tissue concentrations of mAbs relevant to their pharmacologic effects. Therefore, knowledge of tissue distribution kinetics is important to better understand their pharmacokinetics and pharmacodynamics. The tissue distribution of mAbs is affected by many physiologic factors that may be altered in disease status. In the present work, we studied the tissue distribution kinetics of the fusion protein etanercept in inflamed joint tissues and examined the impact of inflammation on the tissue distribution of etanercept. Etanercept concentration profiles in plasma, blister fluid, and different tissues were obtained from healthy and collagen-induced arthritic (CIA) rats by use of a fluorescence quantification method via IRDye800CW labeling. Stepwise minimal and full physiologically based pharmacokinetic (PBPK) approaches were applied to characterize the distribution kinetics of etanercept in tissues in healthy and diseased animals. Etanercept exhibited modest tissue access (tissue/plasma area under the concentration curve [AUC] ratios 0.03-0.15 and estimated tissue reflection coefficients [s] of 0.6-1.0), but with good penetration into arthritic paws (tissue/ plasma AUC ratio 0.23 and s 0.36). Etanercept exposure in the inflamed paws of CIA rats was approximately 3-fold higher than in normal paws taken from either CIA or healthy rats (tissue/plasma AUC ratios 0.23 versus 0.07 and s 0.36 versus 0.71). The tissue distribution kinetics of etanercept in arthritic paws were well characterized with PBPK modeling approaches. Etanercept shows good penetration to arthritic paws in CIA rats. Our study indicates that inflammation produced increased tissue distribution of etanercept in CIA rats.

show abstract

Section: Discussionmentioning

confidence: 93%

Biodistribution of Etanercept to Tissues and Sites of Inflammation in Arthritic Rats

Chen¹,

DuBois²,

Almon³

et al. 2015

Drug Metab Dispos

View full text Add to dashboard Cite

show abstract

“…On the other hand, the V p was similar for control and pioglitazone-treated animals. Although a 2CM estimates V c and CL t similar to physiologically relevant volumes (28), there is the assumption that the clearance is only from the central compartment. Thus, V p values are limited in identifiability, and as such the significance of V p changes may not be physiologically relevant (29).…”

Section: Discussionmentioning

confidence: 99%

Effect of Type 2 Diabetes Mellitus and Diabetic Nephropathy on IgG Pharmacokinetics and Subcutaneous Bioavailability in the Rat

Chadha

Morris

2015

AAPS J

Self Cite

View full text Add to dashboard Cite

Abstract. The objective of this research was to assess the effects of type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN) on the pharmacokinetics of human IgG (hIgG), an antibody isotype, in Zucker diabetic fatty (ZDF) rats. Furthermore, the specific role of T2DM in the altered disposition of hIgG was evaluated by treating diabetic rats with pioglitazone, while the role of chronic kidney disease (CKD) was assessed using 5/6 nephrectomized Sprague Dawley rats. ZDF male (lean non-diabetic control and obese diabetic) and pioglitazone-treated ZDF rats were studied at ages 12-13 weeks (only DM was present), and at ages 29-30 weeks (progression to DN). All animals were dosed with 1 mg/kg of hIgG intravenously (IV) or subcutaneously (SC). ZDF rats had significantly higher blood glucose concentrations and urinary albumin excretion compared to control rats. Significant increases in total clearance (2.5-fold) and renal clearance (100-fold) of hIgG were observed; however the major increase in total clearance was due to increased non-renal clearance. Greater changes in urinary albumin excretion and total and renal clearances of IgG (3.5-fold and 300-fold, respectively) were observed with progression to DN. SC bioavailability of hIgG in all animal groups was similar (>84%). With pioglitazone-treatment, diabetic animals remained euglycemic and treatment was able to reverse the clearance changes, although incompletely. In the CKD group, no difference in hIgG clearance was observed when compared with controls. In conclusion, the increased clearance of hIgG in ZDF diabetic animals, reversal by pioglitazone treatment and lack of effect of CKD, demonstrate the influence of T2DM on hIgG pharmacokinetics.

show abstract

“…Subcutaneous chemotherapy targeted to regional lymph nodes increased lymph node drug concentration compared with intravenous delivery (165), although this method has yet to be tested in a spontaneous model of lymph node metastasis. Lipid nanoparticles also increased delivery of antiretroviral drugs to lymph nodes of primates (166).…”

Section: The Growth Of Lymph Node Metastasesmentioning

confidence: 99%

The Lymphatic System in Disease Processes and Cancer Progression

Padera

Meijer

Munn

2016

Annu. Rev. Biomed. Eng.

186

139

View full text Add to dashboard Cite

Advances in our understanding of the structure and function of the lymphatic system have made it possible to identify its role in a variety of disease processes. Because it is involved not only in fluid homeostasis but also in immune cell trafficking, the lymphatic system can mediate and ultimately alter immune responses. Our rapidly increasing knowledge of the molecular control of the lymphatic system will inevitably lead to new and effective therapies for patients with lymphatic dysfunction. In this review, we discuss the molecular and physiological control of lymphatic vessel function and explore how the lymphatic system contributes to many disease processes, including cancer and lymphedema.

show abstract

Pharmacokinetics, Lymph Node Uptake, and Mechanistic PK Model of Near-Infrared Dye-Labeled Bevacizumab After IV and SC Administration in Mice

Cited by 31 publications

References 28 publications

Biodistribution of Etanercept to Tissues and Sites of Inflammation in Arthritic Rats

Biodistribution of Etanercept to Tissues and Sites of Inflammation in Arthritic Rats

Effect of Type 2 Diabetes Mellitus and Diabetic Nephropathy on IgG Pharmacokinetics and Subcutaneous Bioavailability in the Rat

The Lymphatic System in Disease Processes and Cancer Progression

Contact Info

Product

Resources

About