Radioactivity single oral dose

Perminks et al. (1987) reported that 80% of a single oral dose of dioctyltin dichloride at 2 mg/kg body weight was excreted in the faeces within 2 days. After 3 days, excretion of radioactivity followed first-order kinetics, with a half-life of 8.9 days. After intravenous administration, 66% of the radioactivity was excreted in the faeces, and a half-life value of 8.3 days was obtained, roughly similar to that of oral administration. Percentages of radioactivity excreted in the urine were 11% and 22% following intravenous and oral dosing, respectively. 

FIGURE 11.2 Loss of flocoumafen residues from quail liver. Depletion of radioactivity from Japanese quail after a single oral dose (14 mg/kg). Data are presented as microgram equivalents of/per gram of tissue and are mean values of two animals. Data collected at day 7 and day 12 were from four animals and three animals, respectively (from Huckle et al. 1989). 

The percentage of the total dose of radioactivity excreted daily in the feces, urine, or expired air over a 21-day period following a single oral dose of TCDD- C is shown in Figure 2. Approximately 30% of the... 

Male rats given single, oral doses of 14 mg/kg [l-14C]tributyl phosphate excreted 50% of the label in urine, 10% in exhaled air as C02, and 6% in the feces within 1 day (Suzuki et al. 1984a). Within 5 days, cumulative radioactivity in urine, exhaled C02, and feces accounted for approximately 68%, 10%, and 10% of the administered radioactivity, respectively. 

Ohzawa et al [114] studied the absorption, distribution, and excretion of 14C miconazole in male rats during and after consecutive oral administration at a dose of 10 mg/kg once a day for 15 days. During consecutive administration, the plasma concentration of radioactivity reached the steady state on day 4 and was 0.48 approximately 0.52 pg eq./mL at 24 h after each dose. After the final dose, the plasma concentration of radioactivity reached the maximum level of 1.67 pg eq./ mL at 7.5 h and declined with a half-life of about 18.68 h. The area under the curve 24 h was 28.3 pg h/mL, which is close to the area under the curve O-oo of a single oral dose. 

In rats, chlordecone is slowly eliminated in the feces (Egle et al. 1978). Rats given a single oral dose of 40 mg/kg C-chlordecone excreted 65.5% of the administered dose in the feces and 1.6% of the dose in the urine by 84 days (Eg le et al. 1978). Less than 1% of the administered dose was expired as radiolabeled carbon dioxide ( C-CO2) (Egle et al. 1978). Rats fed C-chlordecone (0.2 mg/kg/day for 3 days) excreted 52.16% of the radioactivity in the feces and 0.52% in the urine 25 days post-dosing (Richter et al. 1979). 

In another study, rats received [14C] disulfoton at a single oral dose of 0.2 mg/kg or 1.0 mg/kg or repeated oral doses of 0.2 mg/kg/day for 14 days (Lee et al. 1985). In the rats given a single dose of 0.2 mg/kg, the respective percentages of administered radioactivity 72 hours later in lemales and males were 97.1% and 96.9% in urine and 1.1% and 1.4% in feces. In the rats given a single dose of 1.0 mg/kg, the respective percentages of administered radioactivity for females and males were... 

Only 6% of the radioactivity from radiolabeled ( "C) heptachlor was found in the urine while 60% was found in the feces of male rats 10 days after a single oral dose indicating that most of the radioactive material was not absorbed and was excreted in the feces (Tashiro and Matsumura 1978). These data strongly suggest that a large percentage of heptachlor is absorbed from the gastrointestinal tract and eliminated via the bile into the feces. More than 72% of the radioactivity eliminated in the feces was present as metabolites of heptachlor (heptachlor epoxide, 13.1% H-2, < 0.1% 1-OH-chlordene, 19.5% 1-OH-chlordene epoxide, 17.5% 1,2-OH-chlordene, 3.5% H-6, 19.0%). 

The major fecal metabolites in male rats administered a single oral dose of "C-heptachlor are heptachlor epoxide, 1-exo-hydroxychlordene, 1-exo-hydroxy-2,3-exo-epoxychlordene, and 1,2-dihydroxydihydrochlordene, as well as two unidentified products (Figure 2-2) (Tashiro and Matsumura 1978). By day 3, 50% of the dose was excreted in the feces. About 72% of the radioactivity was eliminated in the feces in the form of metabolites and 26.2% as parent compound by day 10. The same metabolites were identified in the comparative in vitro study using rat and human microsomal preparations (Tashiro and Matsumura 1978). Heptachlor epoxide is metabolized one step further to a dehydrogenated derivative of 1-exo-hydroxy-2,3-exo-epoxychlordene. Less than 0.1 % of radiolabel was seen of this compound in an in vitro study using human liver microsomes (Tashiro and Matsumura 1978). 

The elimination of a single oral dose of C-heptachlor in male rats showed that most of the radioactivity was eliminated in the feces (Tashiro and Matsumura 1978). One day after dosing, 36% of the dose had been eliminated, and by day 10, approximately 62% had been eliminated in the feces. Elimination of the radioactive label in urine accounted for only 6% of the total dose in 10 days. Approximately 26.2% of the total radioactivity recovered from the feces was the parent compound and the remainder was in the form of metabolites. 

Male Wistar rats given single oral doses of 10, 50, or 250 mg/kg of1,4-dichlorobenzene (vehicle not given) excreted the majority of derived from 1,4-dichlorobenzene in the urine as either the sulfate conjugate (60%) or the glucuronide (30%). Bile contained 5 and 30% of the total radioactivity after the low and high doses, respectively. Only minor amounts of mercapturic acid were found (Hissink et al. 1997). 

No studies were located regarding excretion following oral exposure to 1,3,5-TNB in animals. Following administration of a single oral dose of C-1,3-DNB to rabbits and rats, radioactivity accounting for more than 80% and 63% of the dose, respectively, was excreted in urine, indicating that the main route of excretion is via the urine (Nystrom and Rickert 1987 Parke 1961). Elimination of 1,3-DNB metabolites in urine was rapid and occurred within 48 hours. The major urinary metabolites in rabbits were 2,4-diaminophenol, 1,3-phenylenediamine, and 1,3-nitroaniline (Parke 1961). 

Table I. Excretion of radioactivity via respiration gases, urine, and feces by rats treated with a single oral dose of C-phosfolan.

Table II. Radioactivity levels In tissues of rats following a single oral dose of 2 mg/kg C-phosfolan.

When sheep were given a single oral dose of 9 mg radiolabeled morantel/ kg bw, the amounts of radioactivity in muscle, fat, liver, and kidney, were 20, 20, 1130, and 190 ppb morantel equivalents, respectively, at 7 day after dosing. At 14 days, radioactivity levels were still high in liver and kidney, amounting to 1050 and 80 ppb, respectively. 

When dairy cows were treated with a single oral dose of 5 mg radiolabeled morantel/kg bw, total radioactivity in milk peaked at 84 ppb at the second milking to decline thereafter to 49 ppb and 19 ppb at the fourth and sixth milking, respectively. 

Following administration to rat, dog, rabbit, and cow, clenbuterol was rapidly eliminated, being largely excreted in urine in the form of the parent drug (15). Following a 4 day treatment of cattle at the therapeutic dosage (0.8 g/kg bw) and a 7 day withdrawal, concentrations of clenbuterol in liver were at the level of 0.35 ppb or below, whereas concentrations in urine were approximately one-tenth of the levels in liver (16). Administration, on the other hand, of a single oral dose of radiolabeled clenbuterol to cattle showed that 40% of the urinary radioactivity was due to the parent compound. The urinary half-life of clenbuterol in cattle, estimated from the urinary excretion of the parent compound, was approximately 36 h (17). 

Ractopamine is extensively and rapidly absorbed in turkeys and swine. In swine, radiolabeled ractopamine was excreted at a rate of 88% in urine and 9% in feces. Tire parent compound accounted for 4-16% of the total urinary radioactivity following a single oral dose of ractopamine, but this could increase to 36-85% after repeated dosing (46). In turkeys, only 8% of an oral dose of ractopamine was excreted unchanged in the urine (47). Biliary excretion was observed to be of major importance in turkeys treated with ractopamine, but it was of less importance in swine in which 88% of the oral dose was eliminated in the urine. 

In rats receiving a single oral dose of bis(2-chloro-l-methylethyl)ether of 0.0002-300 mg/kg bw, peak blood levels of radioactivity were reached at about 2-4 h. Following administration of a dose of 30 mg/kg bw, elimination was biphasic in rhesus monkeys, with half-lives of 5 h and two days, and monophasic in rats, with a half-life of two days. In rats, total recovery of radioactivity was 75% of an oral dose of the l- C-labelled compound and 90% after an intraperitoneal dose with the 2-i<-labelled compound approximately 20% of the oral dose was exhaled as CO2 in 48 h. Also in rats, urinary excretion of radioactivity accounted for 48% of a 90 mg/kg bw oral dose of the 1- relabelled compound within 48 h and for 60% of a 30 mg/kg bw intraperitoneal dose of the 2- rC-labelled compound within 24 h. Urinary metabolites identified after administration of an oral dose of 90 mg/kg bw of the I - ( -kibcllcd compound to rats were 2-(2-chloro-1-methylethoxy)propanoic acid (17% of the dose) and N-acetyl-5 -(2-hydroxypropyl)-cysteine (approximately 9% of the dose) following an intraperitoneal dose of the 2- 4C-labelled compound, metabolites identified were l-chloropropan-2-ol, propylene oxide and 2-(2-chloro-l-methylethoxy)propanoic acid (lARC, 1986). 

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