Comparative Pharmacokinetics and Insulin Action for Three Rapid-Acting Insulin Analogs Injected Subcutaneously With and Without Hyaluronidase

• Autores: Linda Morrow, Douglas B. Muchmore, Marcus Hompesch, Elizabeth A. Ludington, Daniel E. Vaughn
• Localización: Diabetes care, ISSN-e 0149-5992, Vol. 36, Nº. 2, 2013, págs. 273-275
• Idioma: inglés
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• Resumen

  • Abstract 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.