Bioavailability absorption, rate

Inhalation bioavailability Absorption rate constant after intranasal administration Fsi % 60.7 5.2 8.5... 

A special case for reduced bioavailabilty results from first-pass extraction that sometimes might be subjected to saturable Michaelis-Menten absorption kinetics. The lower the hepatic drug clearance is (Clhep) in relation to liver blood flow (Ql), or the faster the drug absorption rate constant (Ka), and the higher the dose (D) are, the more bioavailable is the drug (F). 

During absorption of this particular F-PHEA (Mw = 8.6 kD, Mn = 5.3 kD), through the rat lung, transfer occurred at an apparently constant rate of 110 43 ig/h or 3.5 1% of the administered dose per hour. Because mucociliary clearance from the lower airways occurs very slowly (7) these absorption rates convert to substantial bioavailabilities when the absorption process is extrapolated over a 12 h period [(3.5% x 12) or, around 42% may be feasible]. 

In these cases it is not necessary to determine the absolute bioavailability or the absorption rate constant for the product under study. It is only necessary to prove that the plasma concentration versus time curve is not significantly different from the reference product s curve. This is done by comparing the means and standard deviations of the plasma concentrations for the two products at each sampling time using an appropriate statistical test. 

Tronde A, Norden B, Marchner H, Wendel AK, Lennernas H, Bengtsson UH (2003) Pulmonary absorption rate and bioavailability of drugs in vivo in rats structure-absorption relationships and physicochemical profiling of inhaled drugs. JPharmSci 92 1216-1233. 

Absorption/Distribution - Tiagabine is nearly completely absorbed (more than 95%), with an absolute oral bioavailability of about 90%. Food slows the absorption rate but does not altering the extent of absorption. Absorption is rapid, with peak plasma concentrations occurring at approximately 45 minutes after an oral dose. Steady state is achieved within 2 days. 

Absorption/Distribution Following oral administration to HIV-infected patients, the mean absolute bioavailability of zalcitabine was greater than 80%. The absorption rate of a 1.5 mg oral dose was reduced when administered with food. This resulted in a 39% decrease in mean maximum plasma concentrations (Cmax) 25.2 to 15.5 ng/mL, and a 2-fold increase in time to achieve Cmaxfro mean of 0.8 hours under fasting conditions to 1.6 hours when the drug was given with food. The extent of absorption was decreased by 14% (from 72 to 62 ng h/mL). 

Bioavuilubility is a measure of a substance s availability within the body following external exposure. It is mainly governed and influenced by route-specific absorption rates. It may differ between humans and experimental animals. Consequently, if information is available indicating species-specific differences in bioavailability for the same exposure route, the dose descriptor has to be corrected accordingly. 

FIGURE 4.2 A Effect of differences in elimination rate ion the maximum concentration (C, J and time to maximum concentration (F ax) reached after a single oral dose. The drug absorption rate is the same (Ka = 1 h ) for curves A and B. The for curve A is 6 hours the P for curve B is 2 hours. B Differences between absorption rates can have a pronounced effect on the time (T ax) which the maximum concentration (C ,x) reached. Curve A shows an orally administered drug with an absorption rate 4 times faster than that of curve B. Curve C shows the effect of a 50% decrease in bioavailability of drug A. The half-life (4 hours) is similar for scenarios A-C. 

The differences in absorption rate and bioavailability between the tablets prepared with the differing batches of ibuprofen are clearly evident despite the fact that their in vitro dissolution profiles can be practically superimposed when tested according to the USP XXI ibuprofen Tablets monograph. 

Holford NH, Ambros RJ, Stoeckel K. Models for describing absorption rate and estimating extent of bioavailability application to cefetamet pivoxil.Pharmacokinet Biopharm, 1992 20 421-442. 

For many poorly soluble drugs, the dissolution rate best reLects the bioavailability of the compound (Juncher and Raaschou, 1957 Benge et al., 1977). Indeed, solubility might affect absorption only to the extent that it affects the dissolution rate. Since absorption is a dynamic process, the solubility of a drug might be of limited consequence if the absorption rate is so rapid that solubility is not attained in the biological Luid. The dissolution rate in this instance would be critical since it could establish the effective absorption rate (Berge et al., 1977). 

Another technique is to monitor drug or toxicant excretion rather than blood concentrations, especially when blood or plasma concentrations are very low. Using the same equations, the AUC is now replaced by chemical concentrations in urine, feces, and expired air. Some chemicals are primarily excreted by the kidney and urine data alone may be necessary. The rate and extent of absorption are clearly important for therapeutic and toxicological considerations. For example, different formulations of the same pesticide can change the absorption rate in skin or gastrointestinal tract, and not bioavailability, but can result in blood concentrations near the toxic dose. Also different formulations can result in similar absorption rates but different bioavailability. 

The two exponential terms model drug absorption and elimination. The rate of absorption depends on the properties of the drug and is described by kah, the absorption rate constant. The variable F is the bioavailability of the drug and a measure of observed drug exposure relative to an experimental maximum. Bioavailability is more thoroughly described in the next subsection. 

The drawbacks of SC and IM injections include potentially decreased bioavailability that is secondary to variables such as local blood flow, injection trauma, protein degradation at the site of injection, and limitations of uptake into the systemic circulation related to effective capillary pore size and diffusion. The bioavailability of numerous peptides and proteins is, for example, markedly reduced after SC or IM administration compared to their IV administration. The pharmacokine-tically derived apparent absorption rate constant is thus the combination of absorption into the systemic circulation and presystemic degradation at the absorption site. The true absorption rate constant ka can then be calculated as ... 

The equations above apply strictly to dmgs administered as a single IV bolus dose, but for drug administered as an infusion or via oral route, or after multiple dosing, the calculation of AUMC must be adjusted to account for drug input [i. e., infusion time (T) or absorption rate constant JCa and extent of bioavailability F], as shown by Straughn [3]. Although, in theory, AUC will not be affected by the route, the AUMC will be overestimated, and this will result in an overestimation of Vss. 

Bioequivalence Scientific basis on which generic and brand-name drugs are compared. To be considered bioequivalent, the bioavailability of two products must not differ significantly when the two products are given in studies at the same dosage under similar conditions. Some drugs, however, are intended to have a different absorption rate. The FDA may consider a product bioequivalent to a... 

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