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Nasal absorption kinetics of human growth hormone enhanced by acylcarnitines in rats
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Seiya Kagatani*, Noriko Inaba, Muneo Fukui and Takashi Sonobe
Novel Pharma Research Laboratories, Yamanouchi Pharmaceutical Co., Ltd., 180 Ozumi, Yaizu-shi, Shizuoka, 425, Japan
Received 12 June 1997;
revised 21 November 1997;
accepted 23 March 1998.
Available online 30 December 1998.
Abstract
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 Image -carnitine at a high dose of 100 mg/kg in mice. Further, the potential safety of LCC was ten times greater than palmitoylcarnitine chloride.
Author Keywords: Human growth hormone; Nasal absorption enhancer; Acylcarnitines; Lauroylcarnitine; Pharmacokinetic analysis; Single dose toxicity
Purchase the full-text article
References and further reading may be available for this article. To view references and further reading you must purchase this article.
Seiya Kagatani*, Noriko Inaba, Muneo Fukui and Takashi Sonobe
Novel Pharma Research Laboratories, Yamanouchi Pharmaceutical Co., Ltd., 180 Ozumi, Yaizu-shi, Shizuoka, 425, Japan
Received 12 June 1997;
revised 21 November 1997;
accepted 23 March 1998.
Available online 30 December 1998.
Abstract
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 Image -carnitine at a high dose of 100 mg/kg in mice. Further, the potential safety of LCC was ten times greater than palmitoylcarnitine chloride.
Author Keywords: Human growth hormone; Nasal absorption enhancer; Acylcarnitines; Lauroylcarnitine; Pharmacokinetic analysis; Single dose toxicity
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