Masayoshi Tsuji

Skin permeability of various non-steroidal anti-inflammatory drugs in man.

The skin permeabilities of a series of eight salicylates and ten non-steroidal anti-inflammatory drugs were investigated in human subjects. The logarithms of % absorption through intact skin and of n-octanol/water partition coefficients (log P) of the test compounds were plotted against one another, and a parabolic relationship was obtained in both compound series.

Further evaluation of a new penetration enhancer, HPE-101

Abstract— The penetration enhancer, 1‐[2‐(decylthio)ethyl]azacyclopentan‐2‐one (HPE‐101), significantly enhanced the excretion of topically applied [14C]indomethacin when dissolved in dipropylene glycol, triethylene glycol, diethylene glycol, 1,3‐butylene glycol, trimethylene glycol, glycerin, water, silicone or triethanolamine, but not when dissolved in ethanol, isopropyl alcohol, oleyl alcohol, olive oil, peppermint oil, isopropyl myristate or hexylene glycol. HPE‐101 significantly enhanced the excretion of [14C]indomethacin, [14C]nicotinic acid, [14C]5‐fluorouracil, [3H]oestradiol and [3H]triamcinolone acetonide, but not that of [3H]testosterone. HPE‐101 also significantly enhanced the excretion of [14C]indomethacin applied to intact skin of rabbit, guinea‐pig and rat, and to tape‐stripped skin of guinea‐pig, but did not enhance the excretion of [14C]indomethacin applied to tape‐stripped skin of rat or rabbit.

DEVELOPMENT OF TOLERANCE TO 1-(m-TRIFLUOROMETHYLPHENYL)-3-(2-HYDROXYETHYL)-QUINAZOLINE-2, 4(1H, 3H)-DIONE [H-88]

Tolerance was provoked to all the pharmacological activities of H-88 examined, such as anti-inflammatory (Carrageenin-induced rat paw edema), analgetic (Tail pressure method in mice), hypothermic (Rectal temperature in mice), hypomotor activity (Wheal cage method in mice), prolongation of the sleeping time induced by pentobarbital Na (rats and mice), depression of gastric emptying and intestinal transport (rats) and stimulation to hypothalmo-hypophyse-adrenal axis (rats). The effect of H-88 on the pentobarbital Na-induced sleeping time in rats was not dissipated by adrenalectomy, and did not depend on the depression of intestinal absorption. The development of tolerance to H-88 was antagonized by ethionine pretreatment. It is suggested that tolerance to H-88 is mainly due to the hepatic enzyme induction.