Nasal absorption kinetics of human growth hormone enhanced by acylcarnitines in rats

Pharmacokinetic analysis revealed that acylcarnitines enhanced overall nasal absorption of human growth hormone (HGH) in rats. Acylcarnitines dramatically shortened onset time, shortened absorption-duration time, and efficiently delivered HGH. HGH administered intranasally with acylcarnitines appeared in the blood within 0.28–2.7 min, far more rapidly than the 11.7 min after intranasal administration of HGH without acylcarnitines (CTL) or the 9.8 min after subcutaneous administration (SC). Absorption-duration times of HGH enhanced by acylcarnitines were in the range of 2.1–3.8 h, which are shorter than those of CTL (7.5 h) or SC (9.8 h). Among acylcarnitines at 1%, lauroylcarnitine chloride (LCC) showed the greatest absolute bioavailability (17.4%), which is 0.73 times the absolute bioavailability value for SC (22.1%). LCC enhancement reached a plateau at a concentration of 0.1%. This nasal absorption enhancement would be suitable for pulsatile administration. A single dose toxicity study also suggested that LCC had similar systemic safety to L-carnitine at a high dose of 100 mg/kg in mice. Further, the potential safety of LCC was ten times greater than palmitoylcarnitine chloride.