Radioactivity excretion

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. 

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... 

Ward et al. [125] investigated the disposition of 14C-radiolabeled primaquine in the isolated perfused rat liver preparation, after the administration of 0.5, 1.5, and 5 mg doses of the drug. The pharmacokinetics of primaquine in the experimental model was dependent on dose size. Increasing the dose from 0.5 to 5 mg produced a significant reduction in clearance from 11.6 to 2.9 mL/min. This decrease was accompanied by a disproportionate increase in the value of the area under the curve from 25.4 to 1128.6 pg/mL, elimination half-life from 33.2 to 413 min, and volume of distribution from 547.7 to 1489 mL. Primaquine exhibited dose dependency in its pattern of metabolism. While the carboxylic acid derivative of primaquine was not detected perfusate after the 0.5 mg dose, it was the principal perfusate metabolite after 5 mg dose. Primaquine was subject to extensive biliary excretion at all doses, the total amount of 14C-radioactivity excreted in the bile decreased from 60 to 30%i as the dose of primaquine was increased from 0.5 to 5 mg. 

Excretion - The plasma half-life for trospium following oral administration is approximately 20 hours. After administration of oral trospium, the majority of the dose (85.2%) was recovered in feces and a smaller amount (5.8%) was recovered in urine 60% of the radioactivity excreted in urine was unchanged trospium. The mean renal clearance for trospium (29.07 L/h) is 4-fold higher than average glomerular filtration rate, indicating that active tubular secretion is a major route of elimination for trospium. There may be competition for elimination with other compounds that also are renally eliminated. 

Polybrominated Biphenyls. Rats given a single intravenous dose of " C-2,2, 4,4, 5,5 -hcxabromobiphenyl excreted a cumulative 0.96, 3.3, and 6.6% of the dose in the feces 1, 7, and 42 days after dosing, respectively (Matthews et al. 1977). Only traces (0.1% of the dose) were excreted in the urine. Two decay components were calculated from excretion data an initial decay rate of 1.05% of the dose/day and a later rate of 0.15% of the dose/day. Biliary excretion accounted for 0.68% of the dose between 0 and 4 hours after dosing. Analysis of bile and feces showed that at least 95% of the radioactivity corresponded to the parent compound. Moreover, in rats, 35% of the radioactivity excreted in the bile during the first week after a single dosing was reabsorbed (Tuey and Matthews 1980). 

The metabolism of danofloxacin does not differ in swine. When five daily intramuscular injections of 1.25 mg radiolabeled danofloxacin/kg bw were given to pigs, the parent drug accounted for 72-81 % of the radioactivity excreted in feces and urine over the 5- day dosing period (143). In feces, 5-7% of the radioactivity was identified as A-desmethyl danofloxacin. In urine, 2-3% was A-desmethyl danofloxacin, 10-14% danofloxacin-A-oxide, and 3% danofloxacin glucuronide. 

The percentage of administered radioactivity excreted in the urine over a 24 h period in rats decreased with increasing single doses (0.25-8.08 mmol/kg bw 1,2-dichloroethane) administered by gavage in mineral oil (Payan et al., 1993). The authors attributed these results to saturation of metabolism rather than kidney damage, as there were no variations in biochemical parameters of nephrotoxicity between the controls and groups exposed to doses up to 4.04 mmol/kg bw. Urinary levels of thio-diglycolic acid increased as a linear function of the dose of 1,2-dichloroethane until... 

Lee et al. (1975) measured urinary and fecal elimination of 32P in rats after oral administration of labeled white phosphorus. The total radioactivity excreted in urine and feces was assessed in three different groups of rats sacrificed at 4 hours or 1 or 5 days after dosing. Total excretion of 32P was far higher via the urinary route by 4 hours postdosing. Excretion of 32P via the fecal route increased rapidly between 4 hours and 5 days post-dosing. By 5 days post-dosing, combined urinary and fecal excretion accounted for -80% of the administered dose of 32P. 

Iyer et al. (2001) investigated the metabolism of [14C]omapatrilat in humans with samples collected during a clinical study. Plasma samples were prepared from blood spiked with or without methylacrylate to trap compound free sufhydryl groups which was important for this particular compound. Samples were pooled over the 12 subjects enrolled in the study. Urine was pooled over time to give a 0-24 h pooled urine sample representing 92 % of the radioactivity excreted in urine and a 0-168 h sample. Feces was not analyzed. 

The found amounts of radioactivity excreted with the bile are illustrated in the graph in Figure 8. 

During the study period between 6.9 and 7.9% (mean = 7.6 %) of the radioactivity administered were excreted with the bile. The major part thereof was eliminated within the first two hours after injection. The portion of radioactivity excreted with the bile decreased at later measuring intervals. In the last collection interval, i.e. 6-8 h after dosing, an average of 0.09 % of the radioactivity administered was still present in the bile. 

To calculate the portion of administered radioactivity excreted with the milk, it is necessary to know the quantitative milk secretion of each particular rat. However, this is not possible within the present study due to the stress inflicted on the animals by the unusual milking procedure which led to milk retention. Assuming values known from literature (Bornschein (1977)) 6.5 ml per day the portion excreted with the milk can be estimated. 

Animals. 14C-disulfoton is rapidly absorbed, metabolized, and the radioactivity excreted in the urine. The main metabolites are disulfoton sulfoxide and sulfone, their corresponding oxygen analogues and diethylthiophosphate... 

The cumulative C-radioactivity excreted with respiratory carbon dioxide up to 220 h is shown in Figure 5. In Figure 6 the rate of excretion (10 dpm/h) for the time period up to 30 h is presented the peak appears after about 0.5 h. 

The percentage of administered C-radioactivity excreted as respiratory carbon dioxide, with urine and feces, and the total percentage excreted are given in Table I. 

Table I. Percentage of Administered Carbon-14-Radioactivity Excreted with Respiratory Carbon Dioxide, with Urine and Feces, with Respect to Time after Oral Administration of 50 fiCi (1- C) Ascorbic Acid to Guinea Pigs...

The feces in the high-dose animals had 35%, 58%, and 80% ofthe total recovered radioactivity after 24 hours, 48 hours, and 7 days, respectively. The amount of radioactivity excreted in urine was about 10% of amount excreted in feces. A elimination half-life of about 30 hours was estimated for benzo[a]pyrene. The data are limited because the exposed area of skin was not reportedly covered or collars were not employed to prevent ingestion of test compound by the animal. In guinea pigs, 73% of the dose was excreted 7 days after low-level (0.28 mg) exposure to benzo[a]pyrene (Ng et al. 1992). 

Bile, urine, and feces samples for metabolite profiling are collected in 0-8 and 8-24h block collection period or in one 0-24h block collection period. Development stage definitive metabolite profiling and mass balance studies generally involve urine and feces collection in 24 h block periods over 7, 10, or 15 days or until more than 85% of the radioactivity is excreted. Urine and fecal sample time points selected for metabolite profiling generally cover over 90% of the radioactivity excreted in the respective matrix. 

The fraction of the originally injected radioactivity excreted via the lungs decreased from 0.66% to 0.43 % from the 2nd to the 3rd hr. This was a... 

The fraction of the originally injected radioactivity excreted via the lungs decreased from 1.10% to 0.76% from the 2nd to the 3rd hr. There was a drop of 0.34/1.10 or 31 % in the concentration of radioactivity in the expired air. This corresponds to a drop of 35 % in the radioactivity in the expired air of HE, the normal subject. Obviously at this time radioactive carbon dioxide is being formed more rapidlj " in the addict than in the normal subject. 

The metabolism of cocaine was inhibited by SKF-525A, a microsomal enzyme inhibitor. The relationship between the pharmacological activity of cocaine and its derivatives and the inhibitory action on uptake of dopamine into striatal synaptosomes has been studied. [N- " CHsjcocaine was metabolized in healthy humans the production of labelled carbon dioxide provided a measure of N-demethylation, which proved to be greater with lower plasma cholinesterase activity. Radioactivity excreted in the urine was 65-75% in 28 hours, and ecgonine methyl ester proved to be the major metabolite (32-49% of urinary metabolites). 

Figure 16. Semilogarithmic plot of the time course of decline of radioactivity from the whole body, serum, and extravascular pools following intravenous administration of IgG. The radioactivity retained in the body (E + P ) was determined by cumulative subtraction of the radioactivity excreted in the urine from the injected activity. The curve of activity in the extravascular pool (E ) was determined by subtracting the activity in the plasma pool (P ) from that retained in the whole body (E + P ). Reproduced with permission from Waldmann and Strober (1%9) copyright 1%9, S. Karger, AG, Basel.

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