Excretion studies

Arrebola EJ, Martinex Vidal JL, et al. 1999. Excretion study of endosulfan in urine of a pest control operator. Toxicol Lett 107 15-20. 

The earliest reports of controlled release steroids were those of Jackanicz (63), Yolles (64), Anderson (65), and Wise (66). Most of those early studies were based on poly[ (L+)-lactic acid). Implants and granular particles were fabricated with progesterone, norgestrel, and norethisterone. In vivo urinary excretion studies were conducted on [I Cjprogesterone beads (64). The reported results were somewhat questionable as only 20% of the original implanted drug could be accounted for. 

Example. The plot in Fig. 6 was constructed using the data shown in Table 3. Note that the concentration of the drug in each urine specimen is not the information analyzed. The total amount excreted over each time interval and throughout the entire study must be determined. As a result, the experimental details of a urinary excretion study must be very carefully chosen, and strict adherence to the protocol is required. Loss of a single urine specimen, or even an unknown part of a urine specimen, makes construction of an ARE plot impossible. 

In addition, the use of biological monitoring has the advantage that skin penetration under particular conditions of protective clothing is included as well in the approach. The results of a dose-excretion study of propoxur by Meuling et al. (1991) using volunteers indicate a significant increase of the dermal uptake of the compound under conditions of occlusion, where there is increased blood flow, skin temperature, and skin moisture. 

Leng G, Leng A, Kuhn KH, Lewalter J, Pauluhn J (1997) Human dose-excretion studies with the pyrethroids insecticide cyfluthrin urinary metabolite profile following inhalation. Xenobiotica 27 1273-1283... 

In summary, we may say that excretion studies point to the existence of marked differences in specific reaction rates in different individuals and to the probability that each individual exhibits a highly distinctive pattern with respect to his internal chemistry. 

Foreign clinical results are acceptable except in areas where there are immunological and ethnic differences between Japanese and foreigners. The ethnic factors are divided into two components intrinsic factors such as racial factors and physiological differences and extrinsic factors, which include cultural and environmental issues. In these cases, the MHLW may require that some bridging comparative clinical trials be performed with dose ranging protocols. This will enable absorption, distribution, metabolism, and excretion studies to be carried out on Japanese individuals and provide better dosage and indication for the Japanese people. The MHLW also requires that application be accompanied by one year of real-time stability data and that sterility test results be included. 

Boecker BB. 1963. Thorium distribution and excretion studies. Am Ind Hyg Assoc J 24 155-163. 

Boecker BB, Thomas RG, Scott JK. 1963. Thorium distribution and excretion studies. II. General patterns following inhalation and the effect of the size of the inhaled dose. Health Phys 9 165-176. 

In 264 metal grinders analysed for urinary excretion of /V-nitrosodiethanolamine, 166 showed positive results (> 0.5 pg/kg (L)) with levels up to 103 pg/kg (L) urine. The amount of/V-nitrosodiethanolamine in grinding fluids (0.04-90 mg/kg) was predictive of the amounts detected in workers urine. Data from quantitative excretion studies (24-h urines) indicated accumulation of /V-nitrosodiethanolamine during a working week (Spiegelhalder e/a/., 1984, 1987). 

D absorbed is excreted in the urine and because dermal exposure is considered the most likely exposure route ( 1, 2,3). Excretion studies on phenoxy herbicides in man (J3-6) show that 90% of the 2,4,5-T and 75% to 95% of the 2,4-D was excreted unchanged... 

Fumagalli, R., Soleri, L., Farina, R., Musanti, R., Mantero, O., Noseda, G., Gatti, E., and Sirtori, C.R. 1982. Fecal cholesterol excretion studies in type II hypercholesterolemic patients treated with the soybean protein diet. Atherosclerosis 43, 341-353. 

Absorption, distribution, and excretion studied in rats after oral dose tritium labeling also used 421,422... 

Roffey, S. J., Obach, R. S Gedge, J. I., Smith, D. A. What Is the Objective of the Mass Balance Study A Retrospective Analysis of Data in Animal and Human Excretion Studies Employing Radiolabeled Drugs. Drug Metab. Rev. 2007, 39, 17—43. 

Williams DT, Cunningham HM, Blanchfield BJ. 1972. Distribution and excretion studies of octachlorodibenzo-p-dioxin in the rat. Bull Environ Contain Toxicol 7 57-62. 

More recently, partially as a result of increased research sophistication and observations made in ADME (Absorption, Distribution, Metabolism, and Excretion) studies, increased attention is being given to evaluating metabolites of APIs. An old example (not being pursued because of the lack of patent protection) is the metabolite... 

ADME Studies Absorption, distribution, metabolism, and excretion studies were conducted for 24,21,17, and 19 out of the 34 biopharmaceuticals, respectively. No radiolabeled proteins were used for 20, 2,1, and 13 out of the 34... 

Both methods of absorption calculation mentioned are based on the fact that after absorption the drug/metabolites reach the central circulation. In case of oral administered drugs targeting the liver and being eliminated biliary instantly, it is obvious that both methods mentioned fail. In such a special case an absorption estimation might be possible via a biliary excretion study. 

ADME (absorption, distribution, metabolism, excretion) studies... 

Figure 2. Zinc intake and excretion, study 1. Dietary intake is indicated by the top of the bar. The length of the vertical bar represents total excretion in urine and feces. Balance is indicated by the bottom of the bar. When the bottom of the bar is above the zero line, the balance is positive. When the bottom of the bar is below the zero line, the balance is negative.

Figure 4. Zinc intake and excretion, study 2. Dietary intake is indicated by the top of the bar. Balance is indicated by the bottom of the bar.

In the USA, the principal use of atrazine is in agriculture, and the major exposed workers are handlers who mix, load and apply atrazine to row crops. The passive dosimetry studies reported atrazine residues in terms of the parent compound only. The biological monitoring studies measured chlorotiazenes metabolites. The atrazine absorbed dose was back-calculated from the measured metabolites based on a human excretion study. The results of the smdies are reported in Table 1.3 and demonstrate fairly close concordance between the two methodologies. 

Chanarin I, England JM, Mollin C, and Perry J (1973) Methylmalonic acid excretion studies. British Journal of Haematology 25, 45-53. 

Absorption, Distribution, Metabolism, and Excretion. Studies of the pharmacokinetics of... 

Studies regarding the excretion of 1,1-dichloroethane by humans were not available. One study was located in animals regarding the extent or rate of 1,1-dichloroethane excretion. Studies monitoring levels in blood and excretion would be useful to estimate pharmacokinetic parameters. 

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