Giuseppe Mascellani

Rectal absorption of some glycosaminoglycan sulphates and heparin in rats

A standardized extract of glycosaminoglycan sulphates containing heparin, with a low affinity for antithrombin III, and a commercial heparin were administered to rats, by the rectal route. When the glycosaminoglycan sulphates were given in oil emulsion with sodium laurylsarcosinate as surfactant, 1 mg kg−1 and 3 mg kg−1 were sufficient for the clearing and anticoagulant activities respectively. The rectal absorption of glycosaminoglycans after dosing with a suitable ‘promoter produced dose‐dependent effects and their kinetics were comparable to those obtained after intramuscular administration. The oil emulsion improved the bioavailability of glycosaminoglycan sulphates at least 20 times.

EFFECTS OF A SALT OF CHOLESTYRAMINE AND 2‐[4‐(p‐CHLOROBENZOYL)PHENOXY]2‐METHYL PROPIONIC ACID (α‐1081) ON BILIARY LIPID SECRETION IN RATS

1 Hypolipidaemic agents may increase biliary cholesterol in man, inducing a supersaturated bile. 2 To evaluate this possible side‐effect, we have studied bile lipid secretion over a period of 8 h with intact enterohepatic circulation and 4 h with complete interruption in rats treated for two months with a salt of cholestyramine and 2‐[4‐(p‐chlorobenzoyl)‐phenoxy]2‐methyl propionic acid (α‐1081, 1.150 g/kg body wt., daily), cholestyramine (1.125 g/kgbody wt. daily), procetofenic acid (25 mg/kg body wt. daily) and saline respectively (six rats for each group). 3 Cholesterol saturation index significantly (P< 0.005) increased (from 0.21 ±0.01 to 0.39±0.09, mean±s.d.), in rats fed with procetofenic acid but it did not in α‐1081‐ and cholestyramine‐treated animals. 4 Procetofenic acid and, to a lesser extent, cholestyramine increased the bile flow. Procetofenic acid increased cholesterol secretion from 0.45±0.17 to 0.94 ± 0.19 μmol kg−1 body wt. h−1 (mean±s.d.). 5 Cholestyramine increased both serum cholesterol and bile acid secretion from 0.45±0.17 to 0.68±0.10 and 25.8±9.48 to 39.96 ± 6.68 μol kg−1 body wt. h−1 respectively; α‐1081, on the contrary, had no effect on bile lipid secretion. 6 These data suggest that α‐1081 may be used as a new hypolipidaemic drug without any risk of increasing cholesterol in bile.

Urinary Metabolites from (2-Ethyl-2,3-Dihydro-5-Benzofuranyl) Acetic Acid

The identification of urinary metabolites of 2-ethyl-2,3-dihydro-benzofuranyl acetic acid (1a) (prepared by Schiapparelli Research Laboratories (1, 2)) was undertaken as a consequence of discovery of its good antiinflammatory activity and low general systemic toxicity. The search for metabolites was preliminarily restricted to acidic compounds in the reasonable assumption that the acidic function originally present in 1a could not be destroyed. In fact from an acidified urine chloroform extract of treated rats four compounds related to Ia (Fig. 1) could be separated by tlc.