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Absorption of organic anions (phenol red, bromphenol blue and bromosulphonphthalein) has been studied after their application to rat liver surface in-vivo, employing a cylindrical glass cell (i.d. 9 mm, area 0.64 cm2). Every drug appeared gradually in the blood with the peak level at about 1 h, after which its concentration declined slowly. Absorbed model drug was efficiently excreted into the bile. These observations appear to indicate the possibility of drug absorption from liver surface membrane. Absorption ratios of model drugs were estimated to be more than 59 % in 6 h. As to phenol red, its biliary recovery and metabolism ratio did not change as compared with that of i.v. administration.
The Chemical Forms in Which Phenol Red is Secreted into the Bile Of Rats
Summary Rats with ligated renal pedicles and a cannulated bile duct received an intravenous injection of phenol red. Paper chromatography of the bile revealed the presence of two colored substances, one of which was chromatographically identical with phenol red. The other substance could be converted to phenol red by acid hydrolysis and was thus a conjugated form of the dye. The conjugate appeared to be a glucuronide, since it was completely converted to phenol red on treatment with beta-glucuronidase. Within 2 hours after the injection of phenol red, 55% of the dose was excreted in bile as the unchanged compound, and 27% as the glucuronide conjugate. The conjugate, like the parent compound, appeared to be actively secreted into bile.
Effect of butalbital and phenobarbital pretreatment on antipyrine clearance in the rat.
The disposition kinetics of antipyrine after a single i.v. dose (75 mg/kg) of [14C]antipyrine were examined in control rats and in rats pretreated with butalbital and phenobarbital. Blood antipyrine data indicated that daily administration of phenobarbital (50 mg/kg) for 14 days resulted in significantly more rapid elimination of antipyrine than that observed after equal doses of butalbital, which was in turn significantly faster than the control values. Results of additional antipyrine tests after phenobarbital pretreatment for 2 and 5 days showed considerable enzyme induction after only 2 days of exposure to phenobarbital; the mean antipyrine clearance after the 2-day pretreatment was not significantly different from those after the 5- and 14-day pretreatments. The data suggested that the maximum increase in antipyrine clearance, ca. 190% of the control value, was achieved after approximately 5 daily doses of phenobarbital and maintained until the end of the 14-day pretreatment period. The subsequent decline in the induced enzyme activity, assessed by the antipyrine clearance values on days 1, 3, 6, and 9 post-phenobarbital treatment, appeared to be mono-exponential with a half-time of 3.8 days. Thus, the enzyme activity would return to baseline at ca. 15 days after the last dose of phenobarbital. In these studies, consistent increases in liver weight with increasing antipyrine clearance were observed, while no apparent relationship between antipyrine distribution volume and barbiturate pretreatment was found.