Jong Bong Lee1, Beomsoo Shin2, Sang Ho Lee3, Bong Yong Lee3, Tae Hwan Kim1, Min Gi Kim1, Sun Dong Yoo1. 1. School of Pharmacy, Sungkyunkwan University, Suwon, South Korea. 2. College of Pharmacy, Catholic University of Daegu, Gyeongbuk, South Korea. 3. Pharmaceutical Research Institute, Daewoong Pharmaceutical Corporation, Yongin, South Korea.
Abstract
OBJECTIVES: This study was conducted to examine the tissue distribution of human recombinant epidermal growth factor (EGF) after multiple intravenous and subcutaneous injections in mice. METHODS: Male BALB/c mice were divided into (1) EGF 1 mg/kg intravenous dose, (2) EGF 5 mg/kg intravenous dose, (3) drug-free intravenous control, (4) EGF 1 mg/kg subcutaneous dose, (5) EGF 5 mg/kg subcutaneous dose and (6) drug-free subcutaneous control groups. EGF and drug-free dosing solutions were injected by intravenous and subcutaneous injections once a day for 3 days. EGF concentrations in serum and tissues of kidney, liver, lung, small intestine and tongue were determined by ELISA. KEY FINDINGS: As the intravenous and subcutaneous doses were increased from 1 to 5 mg/kg, serum Cmax and area under the concentration-time curve (AUC) values were increased dose-proportionally. In lung, tongue and small intestine, increases in AUC were dose-proportional after intravenous injections, but greater than dose-proportional after subcutaneous injections. The fold-increases in Cmax and AUC values were lowest in liver and highest in kidney. CONCLUSION: Based on Cmax and AUC data, the systemic exposure achieved by subcutaneous injections was comparable with that achieved by intravenous injections.
OBJECTIVES: This study was conducted to examine the tissue distribution of human recombinant epidermal growth factor (EGF) after multiple intravenous and subcutaneous injections in mice. METHODS: Male BALB/c mice were divided into (1) EGF 1 mg/kg intravenous dose, (2) EGF 5 mg/kg intravenous dose, (3) drug-free intravenous control, (4) EGF 1 mg/kg subcutaneous dose, (5) EGF 5 mg/kg subcutaneous dose and (6) drug-free subcutaneous control groups. EGF and drug-free dosing solutions were injected by intravenous and subcutaneous injections once a day for 3 days. EGF concentrations in serum and tissues of kidney, liver, lung, small intestine and tongue were determined by ELISA. KEY FINDINGS: As the intravenous and subcutaneous doses were increased from 1 to 5 mg/kg, serum Cmax and area under the concentration-time curve (AUC) values were increased dose-proportionally. In lung, tongue and small intestine, increases in AUC were dose-proportional after intravenous injections, but greater than dose-proportional after subcutaneous injections. The fold-increases in Cmax and AUC values were lowest in liver and highest in kidney. CONCLUSION: Based on Cmax and AUC data, the systemic exposure achieved by subcutaneous injections was comparable with that achieved by intravenous injections.
Authors: Steve Zaldua; Frederick C Damen; Rohan Pisharody; Riya Thomas; Kelly D Fan; Giri K Ekkurthi; Sarah B Scheinman; Sami Alahmadi; Felecia M Marottoli; Simon Alford; Kejia Cai; Leon M Tai Journal: Heliyon Date: 2020-05-25