Blood levels and urinary excretion

The achievement of adequate serum concentrations and high urinary excretion is an important factor in evaluating the merits of antibacterial compounds. This is particularly true for nitrofurantoin since it is administered most frequently by the oral route. Results of studies in this connection proved to be very favourable 30 to 40 per cent of the administered dosages of nitrofurantoin were excreted in the urine of rats and men [Table 6.20). 

Furazolidone, on the other hand, is excreted in the urine at a very low rate. The amount of nitrofurans found in the bloodstream or in the urine and faeces varies in accordance with the properties of each compound. The administered dose of nitrofurans cannot be totally accounted for by recovery studies. It must be assumed, therefore, that certain body tissues are capable 

Compound Dose oral) mg/kg Plasma concentration (rat) (%) Dose oral) mg/kg Urinary excretion (%)  

Recently, Karasaki studied the blood concentration and urinary excretion of five new nitrofurans containing an oxadiazole ring and five nitrofurans which are commercially available (Table 6.21). These compounds were administered by stomach tube (100 mg/kg in rabbits). 

Compound tested, Concentration in blood (pslmg) Concentration in urine /iglmg) % in urine 6h 

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But many metabolic processes are likely to influence amino acid blood levels and urinary excretion both ways, some of which may be genetically controlled specifically or else may be influenced by a variety of body functions. Endocrine factors have for instance been taken into consideration in the case of histidinuria (S22). It seems, however, that in our present state of knowledge we are still altogether insufficiently informed about amino acid blood levels and on their possible fluctuations. As long as the data published in the literature on amino acidemia remain as scarce as they are at the present time, we feel that our knowledge of the... 

Wagner, J. Nelson, E. Kinetic analysis of blood levels and urinary excretion in the absorption phase after single dose of drug. J. Pharm. Sci. 1964, 53, 1392-1403. 

Griffith RS, Black HR, Brier GL, Wolny JD. Effects of probenecid on the blood levels and urinary excretion of cefamandole. Antimicrob Agents Chemother 1977 11(5) 809-12. 

Slotkin, TA. etal. 1970. Blood levels and urinary excretion ofharmine audits metabolites in man and rats The Journal of Pharmacology and Experimental Therapeutics 173(1) 26-30. 

Beckett AH, Salmon JA, Mitchard M. The relation between blood levels and urinary excretion of amphetamine under controlled acidic and under fluctuating urinary pH values using [ ejamphetamine. JPharm Pharmacol (1969) 21, 251—8. 

Venho VMK, Koskinen R The effect of p3n zinamide, rifampicin and cycloserine on the blood levels and urinary excretion of isoniazid Ann Clin Res (1971) 3,277-80. 

Percutaneous absorption mechanisms - methodology - drug delivery. Marcel Dekker, New York, pp 335-342 Wester RC, Noonan PK, Cole MP, Maibach HI (1977) Percutaneous absorption of testosterone in the newborn rhesus monkey comparison to the adult. Pediatr Res ii 737-739 Yeung D, Kantor S, Nacht S, Cans EH (1983) Percutaneous absorption, blood levels, and urinary excretion of resorcinol applied topically in humans. Int J Dermatol 22 321-324 Young E (i960) Ammoniated mercury poisoning. Br J Dermatol... 

There is now substantial evidence that seborrheic dermatitis (an abnormally oily skin, which results in chronic scaly inflammation) of infants under 5 months of age is due to nutritional biotin deficiency. In such cases, blood levels and urinary excretion of the vitamin are depressed. Prompt improvement occurs with therapeutic doses of the vitamin, about 5 mg/day, given intravenously or intramuscularly. 

This model accurately predicted the time curves for blood concentration and urinary excretion of metabolites by male volunteers exposed to 100 ppm trichloroethylene (Sato et al. 1991). It was found that, while the amount of metabolite excretion increases with body weight, the concentration does not, because of a corresponding increase in urinary volume. Also, women and obese people, compared with slim men, have lower concentrations but longer residence times of blood trichloroethylene because of their higher fat content (Sato et al. 1991). As a consequence, the model predicted that 16 hours after exposure to trichloroethylene, one could expect a woman s blood level to be 30% higher and an obese man s level to be twofold higher than that of a slim man (Sato 1993). 

Participants also expressed concern over techniques for estimating dermal exposure such as the use of patches, and the interpretation of data generated from patch contamination. Patch exposure cannot be correlated with uptake by unprotected skin, nor with blood levels or urinary excretion (except in some cases such as the phenoxy herbicides). Among questions remaining are how to extrapolate the ratio between acute dermal and acute oral doses in animals to man, whether re-entry data will be needed for every pesticide in every crop or crop grouping for every geographic location, and whether humans can legally be used for dermal absorption studies. 

IV. Diagnosis depends on integration of characteristic findings with a history of known or potential exposure and presence of elevated mercury blood levels or urinary excretion. 

Human exposure to environmental contaminants has been investigated through the analysis of adipose tissue, breast milk, blood and the monitoring of faecal and urinary excretion levels. However, while levels of persistent contaminants in human milk, for example, are extensively monitored, very little is known about foetal exposure to xenobiotics because the concentrations of persistent compounds in blood and trans-placental transmission are less well studied. Also, more information is needed in general about the behaviour of endocrine disruptive compounds (and their metabolites) in vivo, for example the way they bind to blood plasma proteins. 

ArterberryJD, Durham WF, ElliottJW, Wolfe HR Exposure to parathion—measurement by blood cholinesterase level and urinary -nitro-phenol excretion. Arch Environ Health 3 476-485, 1961... 

The urinary excretion of DNOC was also studied in these volunteers (King and Harvey 1953b). The 5 volunteers excreted about 7% of the total DNOC dose in the urine over 13 days after exposure. However, only 0.016% of the dose was excreted within 5 hours after exposure and 1.3% within 24 hours after exposure. In the first 24 hours after a single exposure of 75 mg per person, 35.2-46.6% of the dose could be accounted for by blood levels and 0.8-2.0% could be accounted for by urinary levels. Thus, 51.7-64.0% of the oral dose was unaccounted for. These data suggest that DNOC is stored longer in the human body than in the animal body. Since DNOC binds to albumin, the chief internal stores may be extracellular fluids containing albumin. Therefore, urinary levels of DNOC may not be useful biomarkers to quantitate exposure. 

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). 

The Urinary Excretion, Blood Levels, and Production of Ca Steroids. 177... 

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