Percent dose absorbed

The dose may also bind to the application device and not be available for absorption. In these cases a large fraction of the dose may not be thermodynamically driving the diffusion process. Finally, when the dose is applied in solution, saturation may result in precipitation of the chemical. Rapid evaporation of a volatile vehicle may precipitate it, thereby decreasing its availability for absorption. All these factors lead to a phenomenon often seen in dermal absorption studies where percent dose absorbed decreases with applied dose. Conducting a study at high applied doses may underestimate absorption of lower applied doses, and vice versa. Alternatively, for some chemicals dosed in volatile vehicles, evaporation increases thermodynamic activity of the penetrating solute through supersaturation, and enhances absorption. 

The primary purpose for most dermatopharmacokinetic models is to quantitate the linkage between anatomical and physiological properties of skin that play rate-limiting roles in absorption with target sites for which concentrationtime profiles are needed. The complexity of the models is a function of the chemical being studied as well as the level of precision (concentration, time frame) required for the prediction. For example, models created to estimate total percent dose absorbed are much simpler than those designed to predict the time and magnitude of peak plasma concentrations in a subject. 

Note that we define the fraction of dose absorbed as the upper limit of the percent of dose absorbed. Therefore, the percent of dose absorbed changes with time, but the fraction of dose absorbed does not. 

Whole-animal studies assess the percent of the applied dose absorbed into the body using classic techniques of bioavailability, where absorbed chemical is measured in the blood, urine, feces, and tissues with mass balance techniques. Recently, methods have been developed to assess absorption by measuring the amount of chemical in the stratum comeum because it is the driving force for diffusion. Cellophane tape strips are collected 30 minutes after chemical exposure and the amount of drug assayed in these tape strips correlates to the amount systemically absorbed. If the focus of the research is to determine the amount of chemical that has penetrated into skin, core biopsies may be collected and serially sectioned, and a profile of the chemical as a function of skin depth may be obtained. 

Using the above equation to relate the concentration in blood (C, in g/L) to daily intake (d, in g/day) where C = (percent of ingested dose absorbed through the GI tract x percent of that dose absorbed into the blood x the daily amount ingested) divided by (elimination constant x blood volume in a 60 kg female)... 

Percentages refer to the mean percent of the total dose absorbed by subjects ... 

Table 2. Percent of Topically Applied Dose Absorbed Into the Systemic Circulation. 

The shapes of the profiles for the amount absorbed vs. time for F-PHEA with different MWDs have been reported previously (9). In general, the amount of F-PHEA absorbed increases steadily with time although polymers with smaller MWD are absorbed more rapidly. The effect is illustrated in Table I which is reproduced from a previous paper (9). Interpretation of F-PHEA s absorption kinetics can be complicated however, either by varying the administered dose or the administered molecular weight distribution. Table I shows clearly the increasing percent absorbed of a weight averaged F-PHEA of 4.68 kD as the dose was systematically reduced. This data is evidence of the existence of carrier-mediated transfer for F-PHEA in the... 

Recent studies provide evidence for rapid dermal absorption of inorganic lead in adults however, these studies have not quantified the fraction of applied dose that was absorbed (Stauber et al. 1994). The quantitative significance of the dermal absorption pathway as a contributor to lead body burden remains an uncertainty. In children who experience extensive dermal contact with lead in soil, sand, or surface water and suspended sediment (e.g., beach or shoreline exposure scenario), even a low percent absorption... 

Another refinement, that avoids the necessity of developing suitable fecal extraction and chromatographic methods, is to dose the radiolabeled compound by both the i.v. and p.o. routes in two separate studies. Knowing that, by definition, the whole of the i.v. dose must have been bioavailable, a comparison of the proportion of the dose in the urine after the two different routes allows estimation of the percent absorbed. An analogous approach can be used without the use of a radiolabel, when the urine from the two studies is analyzed either for the parent compound or, more usually, for a major common metabolite. Assuming quantitatively identical clearance after both the i.v. and p.o. doses, the ratio of the amounts of analyte in the two experiments gives the absorption. 

The predominant route of excretion in rats is via urine (Gut et al. 1985 Tardif et al. 1987 Young et al. 1977). In rats exposed to 5 ppm of 1- C-acrylonitrile for 6 hours, 68% of the absorbed radioactivity was excreted in the urine within 220 hours, with 3.9% in the feces, 6.1% in expired air as CO2, and 18% of the radioactivity being retained in the body tissues. Following exposure to a higher concentration (100 ppm), a larger fraction of the dose was recovered in urine (82%) and a smaller fraction (2.6%) was retained in the body (Young et al. 1977), indicating that urinary excretion is dose-dependent. Percent fecal excretion was similar at both doses. 

Median Lethal Dosage (LD50) The lethal dose of a poison, when taken orally or absorbed through the skin, which is lethal to 50 percent of the exposed laboratory animal population. 

Incident Dose (mJ/cm2)a Absorbed Dose (mJ/cm2)b Acid Production (mmol)c Percent Conversion (%) Quantum Yieldd... 

Oral- Up to 1000 meg/day. Oral vitamin B-12 therapy is not usually recommended for vitamin B-12 deficiency. The maximum amount of vitamin B-12 that can be absorbed from a single oral dose is 1 to 5 meg. The percent absorbed decreases with increasing doses. 

Diuretic Onset (hours) Peak (hours) Duration (hours) Equivalent dose (mg) Percent absorbed... 

Clinical pharmacology. A bicyclic isobenzofurane derivative, citalopram is nearly completely absorbed after oral administration, with 80% available after first-pass metabolism. Eighty-three percent of that absorbed is protein bound, and peak plasma concentrations are reached in 3 hours (range 1-6 hours] (Milne and Goa 1991]. Even though citalopram s half-life is 33-35 hours, steady-state levels are achieved only after 1-2 weeks, reflecting the longer half-life of its metabolites demethylcitalopram (half-life = 49 hours] and didemethylcitalopram (half-life = 102 hours] (P. Baumann 1992]. Mainly eliminated by hepatic metabolism, citalopram s biotransformation is not fully understood as the parent compound, and its two metabolites account for only 45%-50% of the dose in urine (Van Harten 1993]. 

Zolpidem is rapidly absorbed and has a quick onset of hypnotic action. Bioavailability is 70 percent following oral administration and the drug demonstrates linear kinetics in the therapeutic dose range. Peak plasma concentration is reached at 0.5 and 3 hours. The elimination half-life is short. It is 92% plasma protein bound and is metabolised in liver to inactive metabolites. It is eliminated in the urine and in the faeces. 

All thiazides and related compounds are well absorbed from the GIT and begin to produce diuresis within one hour after oral administration, but the duration is variable, which are due to variation in rates of renal tubular secretion and clearance, metabolism, and enterohepatic circulation. Approximately 50 percent of an oral dose is excreted in urine within 6 hours. Most of the agents undergo little hepatic metabolism and excreted as such. However indapamide is extensively metabolized. 

About 50% of an oral dose of each agent is absorbed. Triamterene is about 60 percent bound to plasma proteins, while amiloride is bound to a lesser extent. Both drugs are secreted in the proximal tubule, presumably by the organic cation secretory mechanism. 

After oral administration, sulfonamides are rapidly and completely absorbed from gastrointestinal tract and approximately 70 to 90 percent of oral dose reaches to the blood stream, but the binding with plasma proteins differ considerably among different groups. The highly plasma protein bound sulfonamides have longer action. The main site of absorption is small intestine. 

It is rapidly absorbed after oral administration. Approximately 40 percent of stavudine appears unchanged in the urine through tubular secretion and glomerular filtration. Nonrenal clearance mechanisms account for about 50 percent of elimination of a dose. 

Zanamivir is delivered directly to the respiratory tract via inhalation. Ten to twenty percent of the active compound reaches the lungs, and the remainder is deposited in the oropharynx. The concentration of the drug in the respiratory tract is estimated to be more than 1000 times the 50% inhibitory concentration for neuraminidase, and the pulmonary half-life is 2.8 hours. Five to fifteen percent of the total dose (10 mg twice daily for 5 days for treatment and 10 mg once daily for prevention) is absorbed and excreted in the urine with minimal metabolism. Potential adverse effects include cough, bronchospasm (occasionally severe), reversible decrease in pulmonary function, and transient nasal and throat discomfort. 

Removal efficiency by high-energy electron beam is usually expressed by G values. The G value is defined as the number of excited states, radicals or other products formed or lost in a system when 100 eV of energy is absorbed (Kurucz et al., 1995b). The G values for each species is shown in the brackets in Equation (12.1). Removal efficiency of solutes can be quantitatively expressed in terms of two constants, GD and k. GD describes the percent removal of solute at a given dose. It is defined by the disappearance of the solute in aqueous solution and is determined experimentally using the following equation (Kurucz et al., 1991) ... 

Apart from physical barriers, topical drug delivery to eye is also affected by the volume, viscosity, pH, tonicity of vehicle, and type of drug. Constant drainage by tear fluid minimizes topical drug absorption and increases systemic absorption. As a result, only about 5 percent of total dose is effectively absorbed through the intraocular route,... 

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