Detail of "55560-96-8"

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Affinity of tixocortol pivalate (JO 1016), tixocortol, cortisol acetate and cortisol for dexamethasone receptors of mouse thymus cells and rat renomedullary interstitial cells in culture

Affinity of tixocortol pivalate (JO 1016), tixocortol, cortisol acetate and cortisol for dexamethasone receptors of mouse thymus cells and rat renomedullary interstitial cells in culture. Correlation with their biological activities. Lelievre, V.; Junien, J. L.; Goyer, R.; Russo-Marie, F. (Jouveinal Lab., Fresnes, Fr.). J. Steroid Biochem., 20(1), 363-6 (English) 1984. CODEN: JSTBBK. ISSN: 0022-4731. DOCUMENT TYPE: Journal CA Section: 2 (Mammalian Hormones) The affinity for the thymocyte dexamethasone [50-02-2] binding sites of tixocortol pivalate (I) [55560-96-8] (a steroid with local antiinflammatory activity similar to cortisol acetate [50-03-3], and with no systemic activity) was compared with that of other steroids. The rank order of relative affinity for dexamethasone receptor of mouse thymocytes (37°) was: dexamethasone (1), cortisol [50-23-7] (0.20), tixocortol pivalate (0.16), tixocortol [61951-99-3] (0.065), and cortisol acetate (0.05). The corresponding 21 oxygenated ester (cortisol pivalate [24869-41-8]) had a lower activity (0.08) for the dexamethanone receptor than did the thiol deriv. (tixocortol pivalate)9. With rat renomedullary interstitial cells in culture, tixocortol pivalate also showed a higher receptor affinity than tixocortol but cortisol acetate was as potent as tixocortol pivalate. The biol. activity of tixocortol pivalate, measured by the inhibition of PGE2 [363-24-6] secretion in the same model, was similar to cortisol acetate and cortisol (38-55% inhibition). Tixocortol was less active (26%). Thus, tixocortol pivalate shows a good correlation between its binding ability and biol. effect.

Comparative pharmacokinetic studies of tixocortol pivalate and cortisol in the rat

Correction of: Comparative pharmacokinetic studies of tixocortol pivalate and cortisol in the rat. Chanoine, F.; Junien, J. L. (Jouveinal Lab., Fresnes 94260, Fr.). J. Steroid Biochem., 21(4), 453-9 (English) 1984. CODEN: JSTBBK. ISSN: 0022-4731. DOCUMENT TYPE: Journal CA Section: 2 (Mammalian Hormones) Comparative pharmacokinetic studies of 14C-labeled tixocortol pivalate (I) [55560-96-8] and 14C-labeled cortisol [50-23-7] were carried out in rats. A 2.5 mg/kg i.v. dose (I or cortisol), a 1 or 25 mg/kg oral dose (cortisol), or a 25, 250, or 1500 mg/kg oral dose (I) was given to male and female rats. 14C radioactivity, [14C]cortisol, [14C]I, and 14C-labeled tixocortol [61951-99-3] were detd. in plasma samples, using TLC detns. and HPLC anal. The plasma clearance and vol. of distribution values of I were 6- and 10-fold larger than those of cortisol, resp. I was rapidly converted into tixocortol, whose plasma concns. were close to those of I. By the oral route, the bioavailability of cortisol was complete, whereas that of I and tixocortol was 0.10-0.20. For the same 25 mg/kg oral dose, plasma values of I and tixocortol were only 1% those of cortisol. Thus, a faster rate of metab., a larger vol. of distribution, and a low oral bioavailability all contribute to the lack of systemic activity of I compared with cortisol.