Urine comparative bioavailability from

Most of the forementioned studies which examined the influence of various dietary fiber on the bioavailability of calcium by human subjects have depended upon the comparative measurements of calcium content of diets and calcium contents of stools and urine. As reviewed by Allen (3), calcium balance studies have distinct limitations relative to accuracy and precision. However, their ease of application and cost, laboratory equipment requirements, and real (or perceived) safety in comparison to available radioactive or stable isotope methods continue to make their use popular. In calcium balance studies, calcium absorption is assumed to be the difference between calcium excretion in the feces and calcium intake. Usually this is expressed as a percent of the calcium intake. This method assumes that all fecal calcium loss is unabsorbed dietary calcium which is, of course, untrue since appreciable amounts of calcium from the body are lost via the intestinal route through the biliary tract. Hence, calcium absorption by this method may underestimate absorption of dietary calcium but is useful for comparative purposes. It has been estimated that bile salts may contribute about 100 g calcium/day to the intestinal calcium contents. Bile salt calcium has been found to be more efficiently absorbed through the intestinal mucosa than is dietary calcium (20) but less so by other investigators (21). 

Oral bioavailability of mibefradil is dose dependent and ranges from 37% to over 90% with doses of 10 mg or 160 mg, respectively. The plasma half-life is 17 to 25 hours after multiple doses, and it is more than 99% protein bound (15). The metabolism of mibefradil is mediated by two pathways esterase-catalyzed hydrolysis of the ester side chain to yield an alcohol metabolite and CYP3A4-catalyzed oxidation. After chronic dosing, the oxidative pathway becomes less important and the plasma level of the alcohol metabolite of mibefradil increases. In animal models, the pharmacological effect of the alcohol metabolite is about 10% compared to that of the parent compound. After metabolic inactivation, mibefradil is excreted into the bile (75%) and urine (25%), with less than 3% excreted unchanged in the urine. 

Adults may receive higher mercury exposures from dermal contact if they work with mercury-contaminated soils. Mercury has been detected in soil and sediment at 350 and 208 sites, respectively, of the 714 NPL sites where it has been detected in some environmental media (HazDat 1998). No experimental information on dermal exposure related to the bioavailability of mercury or mercury compounds sorbed to soils was found. However, Hursh et al. (1989) conducted a study to determine the role of dermal exposure in the uptake of mercury vapor from air. These authors estimated that during an 8-hour day, a person would absorb through the skin only 2.6% of the mercury vapor retained by the lungs exposed to the same atmosphere. These authors also noted that half of the dermal uptake is lost through normal shedding of the stratum comeum. Therefore, dermal uptake of mercury adsorbed to soil is likely to be minor compared to other exposure pathways. Recent information from Hamly et al. (1997) showed that urine mercury levels in a Native American population living near an inactive mercury mine in Clear... 

The concepmal model for As toxicokinetics requires further clarification. Salient features of the model include the following (1) absorbed As is primarily excreted in the urine. Thus, the UEF, defined as the amount of As excreted in urine divided by the dosed amount, can be used to estimate the ABA. (2) Absolute bioavailability (ABA = AF ) of As from a test material can be estimated from the ratio of UEF of As from test material compared with intravenously dosed As. (3) The RBAs of two orally dosed materials (e.g., a test soil and sodium arsenate) can be calculated from the ratio of their UEFs. This calculation is independent of the extent of tissue binding and biliary excretion ... 

The amount of absorbed drug that is ultimately excreted (Ay) can be related to the amount of the absorbed dose. For example, for the same individual, if more drug is absorbed from product A compared to product B, then more drug should appear in the urine. This principle is used in bioavailability studies to determine bioequivalence as a measure of extent of absorption and expressed as relative bioavailability. One requirement of the use of Ay is that enough time is allowed to collect the total amount of the absorbed drug in the urine which is 5 x The experimental procedure and the volunteers that are used in the study also should be the same for products A and B. 

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