The efficiency of intraosseous human growth hormone administration: a feasibility pilot study in a rabbit model

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The use of protein- and peptide-based drugs in the treatment of disease has significantly increased in recent years. However, their chemical and physical properties make them unsuitable for simple oral delivery.


The objective of this proof-of-concept study was to examine the feasibility of protein administered via intraosseous (IO) injection. Human growth hormone (GH), a 22-kd protein, served as the model protein.


An indwelling IO needle and intravenous (IV) line were placed in four New Zealand white male rabbits, and 50, 100, 200, or 400 μg/kg of GH were injected. Blood samples were taken at different time points and analyzed for GH concentration. There were no significant pharmacokinetic differences between the IO and IV routes. For the 400 μg/kg dose, the area under the serum GH concentration time curve was 100.55 ± 46.7 μg/min*mL with IV administration and 84.6 ± 34 μg/min*mL for IO (P = .73 compared to the IV route), Cmax measured 11.2 ± 5 μg/L and Tmax 0.9 ± 0.7 minutes. For the 200 μg/kg dose, the area under the curve was 68.5 ± 16.7 μg/min*mL with IV administration, and 85.1 ± 1.5 μg/min*mL (P = .39) for IO, Cmax measured 8.13 ± 2.44 μg/L and Tmax 1.92 ± 1.06 minutes.


The findings confirm that a large protein (22 kd) can be administered via IO injection, reaching blood levels comparable to IV injection. Further studies with a larger number of animals are required to evaluate the pharmacokinetics and pharmacodynamics of high-molecular-weight proteins injected by the IO route.

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