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We studied the influence of posterior pituitary extract, vasopressin, and somatostatin on hepatic elimination function. Hepatic clearance and its two biological determinants, hepatic blood flow and metabolic activity (clearance Vmax/Km), were determined from hepatic indocyanine green elimination at steady-state in cirrhotic patients. Intravenous infusion of posterior pituitary extract (oxytocin, 59%; vasopressin, 41%) at the constant rate of 0.3 unit per kg per hr decreased hepatic clearance (p less than 0.05) and Vmax/Km (p less than 0.05) but did not change hepatic blood flow. Intravenous infusion of vasopressin (0.3 unit per kg per hr) decreased hepatic clearance (p less than 0.05), Vmax/Km (p less than 0.05) and hepatic blood flow (p less than 0.05). Intravenous infusion of somatostatin (250 micrograms per hr following a bolus i.v. injection of 250 micrograms) decreased hepatic clearance (p less than 0.05), Vmax/Km (p less than 0.05), and hepatic blood flow (p less than 0.05). This study shows that the vasoactive agents used in the management of upper digestive bleeding in cirrhotic patients may have deleterious effects on the metabolic activity of the liver in addition to their effects on hemodynamics. The results suggest that the vasoactive substances either increased the fraction of total hepatic blood which bypassed intact hepatocytes or directly impaired metabolic activity of hepatocytes. Reduction in the metabolic activity of the liver produced by vasoactive agents may have important implications in therapy of portal hypertension.

The pharmacokinetic parameters of fluoride have been studied, after a single oral administration to human volunteers of two fluoridated compounds: sodium fluoride, and a new organic fluoride salt, nicomethanol hydrofluoride. The results obtained with these two compounds were very similar, suggesting that no abnormal accumulation of fluoride in the body occurs after using nicomethanol hydrofluoride.

The main form of rectal administration of medications is the suppository. The rapidity of release of the active principle in the rectal fluid depends mainly on the physicochemical properties of the vehicle. Absorption per se is influenced by the liposolubility as well as the ionization of the medication, and by the site of its release since only the middle and inferior hemorrhoidal veins avoid the hepatic crossing. For molecules subjected to a major 1st hepatic crossing (lidocaine, propranolol, ergotamine...), pharmacokinetic studies demonstrate that the rectal route enables to obtain a bioavailability which is markedly higher by oral route, and plasma concentrations at a therapeutic level. The use, still experimental, of rectal osmotic pumps, provides balanced plasma concentrations which remain stable during the entire duration of the application. Undesirable side effects related to the administration of drugs via the rectal route, are, most of the time, local ones. The vehicles seem to be responsible for diffuse ano-rectitis. Cases of rectal ulcerations with necrosis have been reported following the excessive use of suppositories containing dextro-propoxyphene or ergotamine.