Comparative Pharmacokinetics and Insulin Action for Three Rapid-Acting Insulin Analogs Injected Subcutaneously With and Without Hyaluronidase
- Linda Morrow, MD1,
- Douglas B. Muchmore, MD2,
- Marcus Hompesch, MD1,
- Elizabeth A. Ludington, PHD2 and
- Daniel E. Vaughn, PHD2⇓
- 1Profil Institute for Clinical Research, Chula Vista, California
- 2Halozyme Therapeutics Inc, San Diego, California
- Corresponding author: Daniel E. Vaughn,
OBJECTIVE To compare the pharmacokinetics and glucodynamics of three rapid-acting insulin analogs (aspart, glulisine, and lispro) injected subcutaneously with or without recombinant human hyaluronidase (rHuPH20).
RESEARCH DESIGN AND METHODS This double-blind six-way crossover euglycemic-glucose-clamp study was conducted in 14 healthy volunteers. Each analog was injected subcutaneously (0.15 units/kg) with or without rHuPH20.
RESULTS The commercial formulations had comparable insulin time-exposure and time-action profiles as follows: 50% exposure at 123–131 min and 50% total glucose infused at 183–186 min. With rHuPH20, the analogs had faster yet still comparable profiles: 50% exposure at 71–79 min and 50% glucose infused at 127–140 min. The accelerated absorption with rHuPH20 led to twice the exposure in the first hour and half the exposure beyond 2 h, which resulted in 13- to 25-min faster onset and 40- to 49-min shorter mean duration of insulin action.
CONCLUSIONS Coinjection of rHuPH20 with rapid-acting analogs accelerated insulin exposure, producing an ultra-rapid time-action profile with a faster onset and shorter duration of insulin action.
- Received April 26, 2012.
- Accepted July 31, 2012.
- © 2012 by the American Diabetes Association.
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