Estimation of absorption

Estimation of Absorption Effects in Sodium Tungstate Solutions... 

Sodium tungstate solutions, estimation of absorption effects in, 168-170 Soft x-rays, 11... 

Animal model Dose and media3 Absorption (percent of dose) Basis for estimate of absorption Reference... 

Interroute extrapolation. The values for pharmacokinetic variables in the O Flaherty Model are independent of the route of exposure. However, the model does incorporate media-specific estimates of absorption from the gastrointestinal tract. Different exposure scenarios have been evaluated with the O Flaherty Model for children and adults (O Flaherty 1993, 1995a). 

The original proposal of the approach, supported by a Monte Carlo simulation study [36], has been further validated with both pre-clinical [38, 39] and clinical studies [40]. It has been shown to be robust and accurate, and is not highly dependent on the models used to fit the data. The method can give poor estimates of absorption or bioavailability in two sets of circumstances (i) when the compound shows nonlinear pharmacokinetics, which may happen when the plasma protein binding is nonlinear, or when the compound has cardiovascular activity that changes blood flow in a concentration-dependent manner or (ii) when the rate of absorption is slow, and hence flip-flop kinetics are observed, i.e., when the apparent terminal half-life is governed by the rate of drug input. 

Fig. 2.24.1. Comparison of technical data and cost estimates of absorption- and compressor refrigeration plants (data provided by Deutsche Babcock-Borsig A. G., D-13500 Berlin).

As noted above, disagreement has often been observed among different studies on the effects of fiber, phytic acid and protein source on mineral utilization. Some possible reasons include (a) estimates of absorption from single meals (with or without previous consumption of the same foods used in the test meal which may also affect results) may not always be equivalent to results from multi-day balance studies, (b) in balance studies, the failure to allow sufficient time (e.g., 1-2 weeks or more) for adaptation may alter the findings, (c) variations in the compositions of meals or diets, including mineral levels, between studies may influence the results obtained, and (d) the persons used as subjects vary and this may have an affect. In addition, in the fiber studies, the levels, types, and particle size of fiber fed have varied widely and levels of other possibly confounding components (e.g., caffeine, tanins, oxalates) may have differed. 

Lennernas s group at Uppsala has performed extensive studies to confirm the validity of this in vivo experimental set-up at assessing the rate and the extent of drug absorption. Recovery of PEG 4000 (a non-absorbable marker) is more than 95%, which indicates that the absorption barrier is intact. In addition, maintenance of functional viability of the mucosa during perfusion has been demonstrated by the rapid transmucosal transport of D-glucose and L-leucine. Estimation of absorption half-lives from the measured Pefr agree well with half-lives derived from oral dose studies in humans (i.e. physiologically realistic half-lives). Human Peff estimates are well correlated with the fraction absorbed in humans, and served as the basis for BCS development, and hence the technique is ultimately the benchmark by which other in situ intestinal perfusion techniques are compared. The model has been extensively used to... 

Corrigan OI, Gubbins RH and O Driscoll CM (2003) Estimation of Absorption Parameters from the Non-Steady-State Phase in the Rat Gut Perfusion Model. J Pharm Pharmacol 55 pp 487-493. 

Pithavala YK, Soria I and Zimmerman CL (1997) Use of the Deconvolution Principle in the Estimation of Absorption and Pre-Systemic Intestinal Elimination of Drugs. Drug Metab Dispos 25 pp 1260-1265. 

Vermeire et al. (1999) noted that for both extrapolations, the results were hardly influenced by the assumptions made on absorption, indicating that other factors may be important in route-to-route extrapolation and/or the reliability of the estimates of absorption used in the study was poor. Vermeire et al. (1999) also concluded that scientific justification for the application of route-to-route extrapolation was not derived in this smdy and heavily depends on expert judgment. 

Mean Number of Reflections. Estimation of Absorption-Peak Frequency... 

In addition to these calculated estimates of absorption, a specific estimate of absorbed dose can be made by measuring the metabolites of the pesticide in urine. For pesticides on which good data exist on metabolic excretion, it appears that this method is very sensitive. In a study conducted on orchardists (7), metabolites were detected in the urine samples of all workers, and a statistically significant correlation was found between the total 48 hour metabolite output and the total amount of pesticide sprayed. In contrast the same study indicated that the correlation between urinary output and the total spray time was not significant. This supports the point mentioned earlier that it seems reasonable to presume that exposure is related to the total amount available for contact, and that correlating exposure with the spray time may be misleading. 

In case that an essential part of dose is excreted via urine, an estimation of absorption is often done giving the ratio of urine excretion (oral/intravenous) as absorption rate. It should be compared with the ratio of the dose-normalized plasma AUCs (oral/intravenous). 

The estimation of absorption via the ratio of dose-normalized plasma AUCs after oral and intravenous administration is based on the assumption that ... 

The estimation of absorption based on the urine excretion ratio (oral/intravenous) should be compared with the ratio of dose-normalized plasma AUCs after iv. and oral administration from the rat radiokinetic study. In case of major differences between both methods of absorption determination, a thorough investigation/discussion of a route of administration-dependent metabolism and/or volume of distribution might help to explain the apparent discrepancy. 

Estimates of absorption into the blood were derived from the excretion data of uranium mill workers (Wrenn et al. 1985). They estimated the daily mean absorption of inhaled uranium by mill workers at 24 pg U/day (0.34 pg U/kg for 70-kg reference man) based on measured excretion in feces and workplace ambient air concentrations. The absorption of uranium by these workers was estimated as 0.76% (range, 0.4-1.6%). Control subjects in a study of differential metabolism of °Th, and inhaled in uranium ore dust included 3 retired uranium mill workers (4—14 years since last employment as uranium ore crushermen), and 3 volunteers who lived in uranium milling communities but had no uranium work history. Two consecutive 24-hour urine and fecal collections were obtained and analyzed for and The apparent total intakes of uranium of these individuals ranged from 11 to 18 pg... 

Some of these factors are so variable and so difficult to determine that one may expect at best only approximate estimates of absorption rates. For this purpose the following equation was developed ... 

Mahmood 1. Estimation of Absorption Rate Constant (Ka) following Oral Administration by Wagner-Nelson, Loo-Riegelman, and Statistical Moments in the Presence of a Second Peak. Drug Metab Drug Interact 2004 20 85—100. 

Summary of Estimates of Absorption of Ingested Strontium in Humans 3-8. Reference Respiratory Values for a General Caucasian Population at Different Levels of Activity... 

A Somewhat More Accurate Estimate of Absorption of Solar Radiation by O2... 

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