Urinary production rate

In rats equilibrated with radioiodine-labelled T4 or T3 roughly half of the radioactivity appears as I- in the urine and the other half as free iodothyronines in the feces [12]. Treatment of the rats with 6-propyl-2-thiouracil (PTU) results in a marked decrease in urinary radioactivity and a reciprocal increase in fecal clearance [12]. Also, in humans, PTU has been shown to inhibit peripheral iodothyronine deiodination besides its well-known effect on thyroid hormone biosynthesis [13]. Compared with the rat, deiodination is an even more important pathway for the clearance of thyroid hormone in man as evidenced by the greater proportion undergoing urinary clearance [2]. Furthermore, estimation of iodothyronine turnover kinetics in humans has demonstrated that a major fraction of T4 disposal is accounted for by plasma production rates of T3 and rT3 [2,3],... 

Kraan, P., Dullaart, R., Pratt, J., Wolthers, B., Drayer, N., and De-Bruin, R., The daily cortisol production reinvestigated in healthy men. The serum and urinary cortisol production rates are not significantly different, Journal of Clinical Endocrinoloqy and Metabolism, Vol. 83, No. 4, 1998, pp. 1247-1252. 

In addition to estimation on the basis of urinary metabolic studies, blood production rates of steroids can be estimated, after administration of isotopically labeled steroids, from the specific activity of the unchanged steroids in the blood. This method was extensively used by Tait and coworkers [322,324]. In 1966 a critical survey of steroid hormone metabolism was given by Baulieu [385]. 

Furthermore Tait and co-workers [322] pointed out the marked difference in the urinary and blood production rates of testosterone obtained in women after injection of radioactive testosterone. He concluded that steroids produced from dehydroepiandrosterone contribute little to the blood production rate of androstenedione and testosterone in normal subjects [403]. According to Tait [324], all the blood production rate of androstenedione in the female and testosterone in the male is due to the same secreted steroid, while the blood production rate of testosterone in the female and androstenedione in the male is due about one-half to the same secreted steroid and one-half to converted precursor. The normal male secretes a ratio of testosterone to androstenedione of about 10 1 and the normal female secretes a ratio of androstenedione to testosterone of about 25 1. 

The selective increase in the urinary excretion of an individual low molecular weight protein suggests that its production rate, and thus plasma concentration, has increased dramatically without concomitant glomerular or tubular damage. Examples of this are the urinary excretion of Bence Jones protein in myeloma, lysozyme in some leulcemias, and myoglobin in patients with rhabdomyolysis. 

Chronic liver disease reduces cortisol clearance and the production of urinary metabolites. Cortisol concentrations are elevated by acute ingestion of alcohol. Individuals with alcoholic cirrhosis have normal to elevated basal cortisol concentrations, blunted circadian rhythms, and prolonged clearance rates. 

Estrogens increase tlie plasma concentrations of CBG and thus markedly influence total cortisol blood concentrations. The concentration of free cortisol is unaffected the clearance of cortisol and its production rate and concentrations of urinary metabolites are subnormal with estrogen therapy. 

Malfunction Deficiency Urinary steroids Virilization Aldosterone production rate Blood pressure... 

The mass of endogenous creatinine excreted into the urine, collected over a given time interval (At), is determined. (For each interval, mass creatinine excreted is the product of urinary creatinine concentration times the volume of urine collected.) The mass excreted per rmit time is the rate of creatinine excretion, which is calculated by dividing the mass of creatinine excreted by the time over which it was collected. Next, the mean serum creatinine concentration 0 ) over that interval is calculated from sample determinations this represents the concentration halfway through the interval. In practice, At=24h (1440 min). As (Cs)cr is usually relatively constant, the serum sample is taken at any convenient time. 

Measurement of Urinary Steroid Production Rates Using Stable-Isotopes and GC-MS... 

As Table V indicates, tlie production rate of estrogens during pregnancy is 200--2000 times that in nonprcgmint women, and the urinary excretion of estrogens during jjregnimcy lias a parallel increa.se. 

The usual goal of an oral sustained-release product is to maintain therapeutic blood levels over an extended period. To achieve this, drug must enter the circulation at approximately the same rate at which it is eliminated. The elimination rate is quantitatively described by the half-life (t /2). Each drug has its own characteristic elimination rate, which is the sum of all elimination processes, including metabolism, urinary excretion, and all other processes that permanently remove drug from the bloodstream. 

About two-thirds of the uric acid produced each day is excreted in the urine. The remainder is eliminated through the GI tract after enzymatic degradation by colonic bacteria. A decline in the urinary excretion of uric acid to a level below the rate of production leads to hyperuricemia and an increased miscible pool of sodium urate. 

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. 

C. In adolescent males, testicular testosterone production dramatically rises from prepuberal levels and then declines into adulthood. However, with advancing adulthood there is a drop in the metabolic clearance rate of testosterone, increasing the length of time that testosterone remains in the serum. Evidence of a relatively constant level of serum testosterone is seen in the relative constant levels of urinary 17-ketosteroids, a metabolite of testosterone, from the second to the fifth decade of life. 

The toxicokinetics of 2,4- and 2,6-toluenediisocyanates in 11 chronically exposed workers at two flexible foam polyurethane production plants have been reported. The toluene diisocyanate concentrations in air varied between 0.4 and 4 pg/m in one plant and in the other between 10 and 120 p-g/m. In one of the plants, the plasma 2,4-toluene diamine levels were 0.4-1 ng/mL before a 4-5-week holiday and 0.2-0.5 ng/mL afterwards. The corresponding plasma levels of 2,6-toluene diamine were 2-6 and 0.5-2 ng/mL, respectively. In the other plant, the plasma 2,4-toluene diamine concentrations were 2-23 ng/mL before the holiday and 0.5-6 ng/mL afterwards and those of 2,6-toluene diamine were 7-24 ng/mL before and 3-6 ng/mL afterwards. The plasma concentrations of 2,4-toluene diamine were 2-24 ng/mL before a 12-day holiday, and 1-14 ng/mL afterwards. The corresponding values for plasma 2,6-toluene diamine were 12-29 and 8-17 ng/mL, respectively. The urinary elimination rates for 2,4-toluene diamine before the holiday were 0.04-0.54 and 0.02-0.18 pg/li afterwards. The corresponding values for 2,6-toluene diamine were 0.18-0.76 pg/li before and 0.09-0.27 pg/h after the holiday. The half-life in urine ranged from 5.8 to 11 days for 2,4- and... 

Process analysis looks at the logical sequence in a model where for instance the forecast for a product can be derived from a set of reasonably hard data (such as epidemiological data sets, perhaps of disease incidence, prevalence or death rates). Knowing the numbers of patients suffering from a particular disease such as stress urinary incontinence (SUI), one can state various assumptions which are either fact-based or logical and from this produce a forecast (see Figure 1.2). 

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