Studies on laxatives: biliary and urinary excretion in rats given danthron by intravenous infusion or gastric intubation.
Rats were infused with danthron (I) at doses of 0.48, 2.2 and 5.8 mumol/100 g body weight, or given 12 mumol/100 g with gastric tube. TLC of bile and urine demonstrated a number of metabolites, at both administration routes. These included I monosulphate (II) and -glucuronide (III), two other phase 2 metabolites which behaved as the corresponding diconjugates, and several phase 1 metabolites (IV) in conjugated form. IV as a group were estimated by photometry of hydrolysed samples, using I as a reference. Danthron conjugates as a group were determined in such samples by a specific method for I. Moreover, II and III were determined individually in unhydrolysed specimens. Following infusion, about 80% of the danthron conjugates in bile were excreted after 1 hour; the dose fractions found after 5 hours represented about 20%, 30%, and 40% at the low, intermediate and high dose level, respectively. The corresponding fractions in urine were 16%, 12% and 10%, giving rise to bile:urine excretion ratios of 1.3, 2.7 and 4.0, respectively. This change in excretion pattern was associated with changes in metabolite muster, which involved a decrease in the balance of IV:I conjugates, as well as an increase in III:II ratio. IV was more abundantly present in bile than in urine, and showed a more sustained excretion than the I conjugates. By intragastric administration, the cumulated excretion (bile + urine) of I conjugates were only 6%, 8% and 5% of dose, in three consecutive 6 hours' periods (0-6, 6-12 and 12-18 hours after dosing). The bile:urine excretion ratios seemed to decrease with time, as did the III:II ratio.(ABSTRACT TRUNCATED AT 250 WORDS)[1]References
- Studies on laxatives: biliary and urinary excretion in rats given danthron by intravenous infusion or gastric intubation. Sund, R.B. Pharmacol. Toxicol. (1987) [Pubmed]
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