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• W1833208048 abstract "Metabolism and pharmacokinetics of 1-(2'-trimethylacetoxyethyl]-2-ethyl-3-hydroxypyridin-4-one (CP117) were studied in the rat. Urinary recovery studies were conducted in normal (oral and intravenous) and iron-overloaded rats (500 mg Fe/kg body weight; oral only). In normal rats, the majority of the dose recovered in the urine was as the hydrophilic metabolite, CP102, accounting for 69.7 +/- 9.4% (oral) and 80.7 +/- 7.9% (intravenous) of the administered dose. There was, however, a dramatic decrease in the amount of CP102 recovered (47.7 +/- 5.9%) (p < or = 0.05) in the iron-loaded group of animals. The amount of CP102 glucuronide conjugate recovered in the normal and iron-overloaded rats after oral administration of CP117 did not differ significantly with values of 6.5 +/- 2.5% and 7.1 +/- 2.5%, respectively. There was, however, a significant increase in CP102 glucuronide conjugate (13.7 +/- 3.0%) (p < or = 0.05) after intravenous administration of CP117. Urinary iron content was determined in the iron-overloaded and normal (oral) animals. Negligible levels of the CP117 iron complex and only 0.6 +/- 0.2% was present as the corresponding CP102 complex in the urine of normal animals. Less than 0.1% of the administered dose was recovered as CP117-iron complex and only 1.3 +/- 0.2% as CP102-iron complex in the iron-overloaded animals. Total recovery of the administered dose was significantly different between normal (po) and iron-overloaded groups of animals, decreasing from 76.4 +/- 11.7% to 57.2 +/- 9.6%, respectively (p < or = 0.05). There was no significant difference between the two routes of administration in normal animals, with total recovery of the administered dose of CP117 being 96.1 +/- 9.1% by the intravenous route. Intravenous and oral pharmacokinetics of CP117 was studied in the rat at a fixed dose of 450 mumol/kg. The AUC of the drug was 43.2 +/- 9.1 mumol/liter . hr and 4.1 +/- 1.8 mumol/liter.hr via the intravenous and oral routes, respectively, thus indicating that the systemic bioavailability of the drug is < 10%. Pharmacokinetic parameters of the drug determined by the intravenous route indicate that CP117 has a plasma clearance of 10.9 +/- 3.0 mumol/liter.hr, a mean residence time of 0.14 +/- 0.05 hr, and volume of distribution at steady-state of 1.54 +/- 0.52 liters.kg-1. The Cmax and tmax of CP117 were 12.1 +/- 2.5 mumol/liter and 7.0 +/- 2.7 min, respectively. The AUC of the main metabolite, CP102, decreased from 425.3 +/- 8.5 mumol/liter.hr to 282 +/- 31 mumol/liter.hr via the intravenous and oral routes, which is presumed to reflect differences in hepatic extraction and routes of elimination of the drug. Parallel absorption studies conducted using the in situ isolated rat gut loop model indicate that the majority of the administered dose was absorbed intact as the parent drug with mesenteric vein AUC values of 3.1 +/- 1.7 mmol/liter.hr and 0.3 +/- 0.04 mmol/liter.hr for CP117 and CP102, respectively." @default.
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• W1833208048 title "Metabolism and pharmacokinetics of 1-(2'-trimethylacetoxyethyl)-2-ethyl-3-hydroxypyridin-4-one (CP117) in the rat." @default.
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