PEGylated interferon displays differences in plasma clearance and bioavailability between male and female mice and between female immunocompetent C57Bl/6J and athymic nude mice

Journal of Pharmaceutical Sciences
Cornelia B LandersdorferLisa M Kaminskas

Abstract

Gender and immune status can considerably impact on the pharmacokinetics (PK) of macromolecular and small molecule drugs. However, these effects are often not considered in drug development. We aimed to quantitatively evaluate effects of gender and immune status on the PK of PEGylated interferon in frequently used murine models. Chronically cannulated female athymic nude and female and male immunocompetent C57Bl/6J mice (n = 24 in total) received a single intravenous or subcutaneous (s.c.) dose of PEGylated interferon. Serial blood samples were taken for 48 h. Noncompartmental analysis and population PK modeling with covariate analysis were performed to evaluate the data. The PK of PEGylated interferon followed a three compartment disposition model with two sequential compartments for s.c. absorption. Female nude mice had significantly higher plasma clearance than C57Bl/6J mice (0.503 vs. 0.397 mL/h). Male mice had a slower absorption rate constant (0.138 h(-1)) and extent (46.2%) of s.c. absorption than female mice (0.274 in C57Bl/6J and 0.374 h(-1) in nude, 60.8% in both). Thus, gender and immune status significantly impacted on important PK parameters of PEGylated interferon in murine models commonly utilized in drug develop...Continue Reading

References

Nov 5, 1999·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·K E MogensenG Uzé
Mar 20, 2002·Cytokine & Growth Factor Reviews·Hiroaki IkedaRobert D Schreiber
Jul 1, 2004·Skin Research and Technology : Official Journal of International Society for Bioengineering and the Skin (ISBS) [and] International Society for Digital Imaging of Skin (ISDIS) [and] International Society for Skin Imaging (ISSI)·F MirrashedB Tomanek
Oct 16, 2004·Expert Review of Anti-infective Therapy·Joseph Ahn, Steven Flamm
Aug 31, 2006·British Journal of Clinical Pharmacology·Samir GuptaDavid Cutler
May 21, 2009·Molecular Pharmaceutics·Lisa M KaminskasChristopher J H Porter
Feb 8, 2011·Clinical Pharmacokinetics·Michael N Neely, Natella Y Rakhmanina
Mar 4, 2011·The AAPS Journal·Jurgen Bernd BulittaCornelia Barbara Landersdorfer
May 10, 2011·Journal of Clinical Pharmacology·Matthew M RiggsDaniel S Stein
May 11, 2011·Current Pharmaceutical Biotechnology·Jurgen B BulittaArnold Louie
Mar 14, 2012·Immunology and Cell Biology·Nicole A de Weerd, Thao Nguyen
May 19, 2012·Journal of Controlled Release : Official Journal of the Controlled Release Society·Hiroshi Maeda
May 24, 2012·The AAPS Journal·Wolfgang F RichterMarilyn E Morris
Mar 19, 2013·Journal of Controlled Release : Official Journal of the Controlled Release Society·Lisa M KaminskasChristopher J H Porter
Aug 27, 2013·European Journal of Clinical Pharmacology·C XuV Sniukiene
Mar 7, 2014·Nature·Londa Schiebinger
Apr 29, 2014·The Lancet Infectious Diseases·Jason A RobertsUNKNOWN International Society of Anti-Infective Pharmacology and the Pharmacokinetics and Pharmacodynamics Study Group of the Europe

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Citations

Apr 11, 2015·Journal of Medicinal Chemistry·Douglas E V PiresDavid B Ascher

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