Pigs were administered intramuscularly molar equivalents of
HI-6 salts (
HI-6 dichloride 10.71 mg/kg and
HI-6 DMS 13.59 mg/kg) either with or without
hyaluronidase (60 U/kg).
Hyaluronidase is supposed to increase tissue permeability and diminishes discomfort caused by the
intramuscular injection. Doses of
HI-6 salts corresponded with standard
HI-6 dichloride dose in one autoinjector (500 mg) and were recalculated for 1 kg of
body weight. According to the results, both
HI-6 salts applied in combination with
hyaluronidase had increased tissue absorption and improved pharmacokinetic profile. The Cmax was significantly higher in case of
HI-6 DMS plus
hyaluronidase (29.6 ± 2.98 μg/ml) administration increase compared to
HI-6 DMS (23.8 ± 3.04 μg/ml) and
HI-6 dichloride (19.0 ± 0.93 μg/ml); both without
hyaluronidase. Bioavailability calculated as AUCtotal (
HI-6 DMS with
hyaluronidase, 4,119 ± 647 min μg/ml) was also significantly higher compared to
HI-6 DMS (2,259 ± 329 min μg/ml) and
HI-6 dichloride (1,969 ± 254 min μg/ml); both without
hyaluronidase. The results suggest that administration of
HI-6 salt with higher solubility is the first step in the improvement of application strategy, but use some substances with spreading effect (
hyaluronidase) may also leads to better absorption and better bioavailability. Improved bioavailability could to go hand in hand with increased effectiveness of
therapy without the need of multiple autoinjector applications.