Summary
ZK 36 374, a chemically stable and equipotent prostacyclin analogue, was tritium labelled at position 11 and administered orally or intravenously to rats in doses of 3–200 μg/kg. Excretion of radioactivity via urine, faeces and bile was studied in male and female animals. Enterohepatic recirculation was assessed by bile duct cannulation and by intraduodenal administration of radioactive bile samples. Metabolic patterns were determined by HPLC separation.
Most of the ZK 36 374 was metabolized in the rat and mainly excreted renally (60% of dose) in the form of 12 metabolites. Half-lives of renal and biliary elimination were 0.7–0.8 h in the α-phase. About 60% of the amount excreted via the bile was reabsorbed in the gut. Radioactivity in the urine collected on days 3, 5 and 7 was higher by one order of magnitude than on the preceding days 2, 4 and 6. Variations in the volume of urine as compared to a control group and different clearance rates of metabolites could be excluded as possible explanations for this effect, which still remains to be clarified.
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Schillinger E., in preparation.
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Krause, W., Skuballa, W. & Schulze, P.E. Pharmacokinetics and biotransformation of the prostacyclin analogue, ZK 36 374 I. Synthesis of a tritium marker and excretion of [3H]-ZK 36 374 in the rat. European Journal of Drug Metabolism and Pharmacokinetics 8, 137–144 (1983). https://doi.org/10.1007/BF03188739
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DOI: https://doi.org/10.1007/BF03188739