Urinary excretion data

Figure 20 Urinary excretion data showing the influence of moisture on the percutaneous absorption rate of salicylates. (O) Anhydrous system rate ( ) hydrous system rate. (Reprinted with permission from Ref. 62.)...

Chuiavatnatol, S., Charles, B. G., Determination of dose-dependent absorption of amoxycillin from urinary excretion data in healthy subjects, Br. 

According to a biopharmaceutic expert, the term bioavailability may be defined as the rate and extent to which the ingredient is absorbed from the drug product into the body or to the site of action. It is measured by blood, serum or plasma levels or from urinary excretion data. 

The primary endpoint of the toxicokinetic studies is the concentration-time prohle of the substance in plasma/blood and other biological fluids as well as in tissues. The excretion rate over time and the amount of metabolites in urine and bile are further possible primary endpoints of kinetic studies, sometimes providing information on the mass balance of the compound. From the primary data, clearance and half-life can be derived by several methods. From the excretion rate over time and from cumulative urinary excretion data and plasma/blood concentration measured during the sampling period, renal clearance can be calculated. The same is the case for the bUiary excretion. 

Figure 1. Proposed pathway of diethanolamine metabolism in the rat, based on urinary excretion data from an eight-week oral dosing study (7 mg/kg bw per day, five days per week for eight weeks)...

Way and coworkers. Reviews of metabolism (51) and pharmacokinetics (97) of pentazocine have been published. The effect of route of administration on the disposition of pentazocine has been explored (27, 9,75,85,86). The metabolic pathways available to pentazocine are outlined in Figure 10. Also shown are urinary excretion data for the metabolites expressed as percent of administered dose. 

Urinary excretion data from 15 female and 27 male subjects given 200 pg chromium(III) as chromium trichloride indicated that gastrointestinal absorption was at least 0.4% (Anderson et al. 1983). Net absorption of chromium(III) by a group of 23 elderly subjects who received an average of 24.5 pg/day (0.00035 mg chromium(III)/kg/day) from their normal diets was calculated to be 0.6 pg chromium(III)/day, based on an excretion of 0.4 pg chromium/day in the urine and 23.9 pg chromium/ day in the feces, with a net retention of 0.2 pg/day. Thus about 2.4% was absorbed. The retention was considered adequate for their requirements (Bunker et al. 1984). 

The amount of absorption of chromium(VI) and chromium(III) was measured in four male and two female volunteers (ages ranging from 25 to 39 years) treated orally with potassium chromate (chromium(VI)) or chromic oxide (chromium(III)) in capsules at doses of 0.005 mg/kg/day and 1.0 mg/kg/day, respectively (Finley et al. 1996b). Subjects were exposed to each compound for 3 days. Based on urinary excretion data, mean absorption of potassium chromate was 3.4% (range 0.69-11.9%). No statistically significant increase in urinary chromium was observed during chromic oxide dosing,... 

Urinary excretion data from 5 humans who each ingested 75 mg DNOC/day for 5 days suggested that at least 7% of the dose was eliminated via the urine over a 13-day period (King and Harvey 1953b). Only 0.016% and 0.8-2.0% of the dose were excreted in the first 5 and 24 hours,... 

In vivo experiments on 4 human volunteers, to whom 0.0026 mg/cm2 of 14C-benzene was applied to forearm skin, indicated that approximately 0.05% of the applied dose was absorbed (Franz 1984). Absorption was rapid, with more than 80% of the total excretion of the absorbed dose occurring in the first 8 hours after application. Calculations were based on urinary excretion data and no correction was made for the amount of benzene that evaporated from the applied site before absorption occurred. In addition, the percentage of absorbed dose excreted in urine that was used in the calculation was based only on data from rhesus monkeys and may not be accurate for humans. In another study, 35-43 cm2 of the forearm was exposed to approximately 0.06 g/cm2 of liquid benzene for 1.25-2 hours (Hanke et al. 1961). The absorption was estimated from the amount of phenol eliminated in the urine. The absorption rate of liquid benzene by the skin (under the conditions of complete saturation) was calculated to be low, approximately 0.4 mg/cm2/hour. The absorption due to vapors in the same experiment was negligible. The results indicate that dermal absorption of liquid benzene is of concern, while dermal absorption from vapor exposure may not be of concern because of the low concentration of benzene in vapor form at the point of contact with the skin. No signs of acute intoxication due to liquid benzene dermally absorbed were noted. These results confirm that benzene can be absorbed through skin. However, non-benzene-derived phenol in the urine was not accounted for. 

Half-life. Derived from urinary excretion data, about 10 to 15 hours. 

Half-life. Derived from urinary excretion data, about 16 hours. Reference. F. T. Delbeke and M. Debackere, ibid. 

Half-life. Plasma half-life, oxpentifylline, about 1 hour, 5-hydroxy metabolite about 1 hour l-(3-carboxypropyl)-3,7-dimethylxanthine, derived from urinary excretion data, about 1.4 hours. 

Urinary excretion data was used to estimate the absorption of uranium by workers accidentally exposed to uranium hexafluoride (Fisher et al. 1990). Estimated airborne concentrations were 20 mg uranium hexafluoride/m for a 1-minute exposure and 120 mg uranium hexafluoride/m for a 60-minute exposure (15.2 and 91 mg U/m respectively) (USNRC 1986). Initial intakes of workers involved in the accident ranged from 470 to 24,000 pg uranium. 

Fisher et al. (1991) Biokinetic Model A modified biokinetic model for uranium was developed for inhaled soluble uranium based on human data from an accidental release of uranium hexafluoride in Oklahoma. Urinary excretion data from 31 exposed workers were used to test two previously published compartmental models for inhalation exposure to uranium (ICRP 1979 Wrenn et al. 1989). Urinary uranium was measured periodically for 2 years following the accident. Statistical analysis showed that the Wrenn et al. (1989) model produced a better fit to the excretion data than the ICRP (1979) model. 

Khalafallah, N., Khalil, S. A. and Moustafa, M. A. (1974). Bioavailability of determination of two crystal forms of sulfameter in humans from urinary excretion data. J. Pharm. Set, 63, 861. [246]... 

Regardless of whether the data are analysed by a compartmental or non-compartmental method, the duration of blood sampling and the limit of quantification of the analytical method used to measure the drug concentration are important features of the pharmacokinetic study. The MRT, after an intravenous bolus dose of a drug can be estimated from either plasma drug concentration or urinary excretion data (Rowland Tozer, 1989). 

Urinary excretion data of human subjects indicate that 4-hydroxylation of methamphetamine is much more extensive than that of amphetamine the metabolic ratio (total hydroxymethamphetamine/methamphetamine) in urine averaged about 15 with individual variations of approximately fiftyfold (Shimosato 1988), suggesting considerable importance of CYP2D6 polymorphism in the fate of methamphetamine. On the other hand, there seems to be no information on the further metabolism of p-hydroxymethamphetamine as is available for p-hydroxyamphetamine. 

J. G. Wagner and E. Nelson, Percent absorbed time plots derived from blood level and/or urinary excretion data. / Pharm Sci 52 610-611 (1963). 

Silber, R. H., Estimation of hydrocortisone secretion. Method of calculation from urinary excretion data. Clin. Ckem. 1, 234r-240 (1955). 

Metabolites of tea catechins are excreted in bile or urine. In general, small conjugates, such as monosulfates, tend to be excreted in urine, and extensively conjugated metabolites are more likely to be excreted in bile. The total amount of metabolites excreted in urine correlated roughly with maximum plasma concentrations. " The exact half-lives of tea catechins in plasma were calculated to be in the order of 2-3 h, except for EGCG, which is eliminated more slowly. " Relative urinary excretion data were used to estimate the minimal absorption rate and were consistent with the plasma kinetic data for most catechins, but for EGCG that mostly excreted in bile, the urinary excretion rate was very small (0-0.1%), and its absorption was underestimated. The urinary excretion rates of EC and EGC were 18.5 and 11.1%, respectively. The low cumulative excretion of tea catechins in human urine, which was 0-9.8%, suggested that they were extensively metabolized in the human body. 

N7. Nordin, B. E. C., and Fraser, R., A calcium-infusion test 1. urinary excretion data for recognition of osteomalacia. Lancet i, 823-826 (1956). 

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