ESPE Abstracts (2015) 84 FC-LB3

Pharmacokinetic and Pharmacodynamic Studies of Topicon Mediated Patch Delivery of Insulin Glargine in a Streptozotocin-Induced Hairless Rat Model

Stephen Hsu, Carl Mangleburg & Hua Yao


Prometheon Pharma, LLC, Alachua, Florida, USA


Background: The Topicon™ patch is a needle-free novel platform technology developed to achieve truly passive transdermal delivery of insulin. Here we report pharmacodynamic (PD) and pharmacokinetic (PK) studies comparing needle injection (s.c.) vs Topicon™ mediated patch delivery of the insulin analog glargine (LANTUS®) in streptozotocin-induced hairless rats.

Objective and hypotheses: We sought to develop a convenient, affordable, and needle-free transdermal patch formulation capable of achieving passive delivery of large molecule drugs such as insulin and insulin-analogues for multiple days.

Method: Male CD® hairless rats were induced with type 1 diabetes (T1DM) by i.p. injection of streptozotocin (65 mg/kg). Plasma insulin glargine was determined by ELISA (Mercodia Iso-Insulin Kit). PK calculations are based on extravascular non-compartmental analysis (NCA) using PKSolver 2.0 for Microsoft Excel. The first-order elimination rate constant (Kel) was calculated as 0.693/T1/2. Required input rate of insulin (k0) to reach Cmax was calculated by Cmax*Vd*Kel)/(1−e^Kel*t). Amount of LANTUS® delivered by Topicon™ patch per unit surface area over time (t) was Jss*t, where Jss is the steady-state flux rate.

Results: A single s.c. injection of 10 U/kg of LANTUS® resulted in an unexpectedly rapid rise to a peak plasma glargine concentration (Cmax) of ~120 mU/ml at 1 h, rapid elimination with plasma half-life (t1/2) of 2 h and a return to baseline level by 5 h. Blood glucose (BG) lowering was observed from baseline mean of ~375 mg/dl to ~70–80 mg/dl for 0.5–5 h. Administration of LANTUS® 20 U/kg in a 1 cm2 patch resulted in a Cmax of 5.3 mU/ml at 2 h, a t1/2 of 1.7 h. Euglycemia was achieved in 4 h and maintained for 6–7 h. PK modeling was done to assess whether a Topicon™ glargine patch can achieve a clinically meaningful therapeutic response by combining in vitro EpidermFT™ permeation data with the reported Cmax of 22 mU/ml at 12 h after injection of LANTUS® 0.4 mg/kg in T1DM.

Conclusion: Our in vivo studies support the feasibility of developing an effective Topicon™ extended-wear basal insulin patch that can achieve BG lowering comparable to s.c. injection. Within 10 h, a 3×3 cm2 patch containing ~200 U of LANTUS® can achieve and maintain a target Cmax of 22 mU/ml continuously for >7 days.

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