First-pass loss

Kunta JR, Lee SH, Perry BA, Lee YH and Sinko PJ (2004) Differentiation of Gut and Hepatic First-Pass Loss of Verapamil in Intestinal and Vascular Access-Ported (IVAP) Rabbits. Drug Metab Dispos 32 pp 1293-1298. 

Although drugs administered by inhalation bypass the hepatic first-pass effect, the lung may also serve as a site of first-pass loss by excretion and possibly metabolism for drugs administered by nongastrointestinal ("parenteral") routes. 

Most opiates are subject to significant first-pass metabolism in the liver, and for this reason, parenteral administration is more effective than per os, although the latter is often of longer duration.07 418 At therapeutic plasma levels, about one-third of the drug is bound to plasma protein. Codeine, which has the morphine 3-OH masked, behaves rather differently, and because of a lower first-pass loss, has a significantly greater po efficacy (about two thirds the parental effect). 

Another type of early clinical study may be conducted with the primary objective of establishing the bioavailability of a particular dosage form, concentration, and regimen. Bioavailability can be defined as the proportion of an administered dose that reaches the systemic circulation in an unchanged form. Maximum bioavailability results after an intravenous injection of the drug. In this case, the bioavailability is by definition 100%. When administered orally, however, a drug experiences first-pass metabolism, also called first-pass loss, before it reaches the systemic circulation. 

Indirect method / , can be estimated indirectly from IV/PO PK of cold compounds with the following assumptions (1) liver is the major organ for elimination, (2) linear PK, (3) plasma concentration is the same as blood concentration, and (4) there is no gut first-pass loss. 

Kunta, J. R. et al., Differentiation of gut and hepatic first-pass loss of verapamil in intestinal and vascular access-ported (IVAP) rabbits, Drug Metab. Dispos., 32(11), 1293, 2004. 

In the diacid mediod, die PA salt is made first. A solution of this PA salt in water can be used for the polymerization. In the temperature range where the reaction rates are high, the diamines are volatile, and thus, it is preferable to carry out the prepolymerization under pressure. The prepolymerization can be carried out either at 220-250°C for 1 h or at 280-320°C in a matter of seconds. In the latter case, die reaction is carried out in a small-diameter tubular reactor.64 Although a prepolymerization under pressure is preferred, Nielinger28 has described a polymerization at atmospheric pressure at 210°C, whereby the loss in diamine is compensated for. 

The performance of a reactor for a gas-solid reaction (A(g) + bB(s) -> products) is to be analyzed based on the following model solids in BMF, uniform gas composition, and no overhead loss of solid as a result of entrainment. Calculate the fractional conversion of B (fB) based on the following information and assumptions T = 800 K, pA = 2 bar the particles are cylindrical with a radius of 0.5 mm from a batch-reactor study, the time for 100% conversion of 2-mm particles is 40 min at 600 K and pA = 1 bar. Compare results for /b assuming (a) gas-film (mass-transfer) control (b) surface-reaction control and (c) ash-layer diffusion control. The solid flow rate is 1000 kg min-1, and the solid holdup (WB) in the reactor is 20,000 kg. Assume also that the SCM is valid, and the surface reaction is first-order with respect to A. 

Invented by H.E. Benson in 1952 and then developed with J.H. Field at the U.S. Bureau of Mines. First licensed by the Benfield Corporation of Pittsburgh, PA, subsequently acquired by the Union Carbide Corporation, and now licensed by UOP. The current UOP version includes new solution activators and incorporates zeolites or membrane processes for complete separation of acid gases and minimal loss of product gases. More than 675 plants were operating in 2000. Variations include the Benfield UiPure process and the Benfield LoHeat process. See also Carsol, CATACARB, Giammarco-Vetrocoke, UiPure. 

Figure 9.22 Storage and loss moduli G and G" for a water-in-oil emulsion containing 99% water, 0.5% C10H22 oil, and 0.5% trethylcnc glycol dodecyl ether (C12EO3) surfactant at 40°C. The droplets are around a micron in size. The closed circles ( ) are for the first experimental run, while the open circles (Q) are for a repeat run. The solid and dashed lines are fits of the Maxwell model to the first and second runs, respectively. The fitted modulus Goo is 216 Pa for both runs, while the fitted relaxation times are 2.7 sec and 4.3 sec. (Reprinted with permission from Pons et al.. Journal of Physical Chemistry 97 12320 Copyright 1993, American Chemical Society.)...

Starting from 15, two retention pa ways exist clockwise (15 23- 4- 25-> 13->-24), and counterclockwise (15- -24). If it is assumed that, in the reaction under discussion, the rate of loss of L4 is fast compared to the rates of pseudorotation, the clockwise mechanism becomes the pathway for inversion. In summary, the initial phosphorane 15 faces three alternatives. The first pathway (15- 34) is blocked by ring strain, and the second (15->23) by the unfavorable "1 placement of both relatively electronegative ligands in... 

To operate a stirrer, knowledge is in the first instance required concerning the required power input Pm of the electrical motor. This has to take into account both the stirrer power and all power losses Py in the shaft bearings, in the gear box and in the shaft seals. In addition the start up power Pa has to be included. This considerably depends upon the stirrer type and upon the type of drive (stirrer shaft rigidly or elastically coupled with the motor shaft belt drive) ... 

We can see from these equilibria that L-ascorbic acid is a moderately weak acid in the loss of the first hydrogen ion and a very weak acid in the loss of the second. The pA"a for dehydroascorbic acid is only a rough value. The radical, HA, however, is a strong acid, comparable with the mineral acids. Of course all these species have their own redox behaviour values of the reduction potentials which have been determined or estimated for these moieties are shown in equations... 

Monomeric amines have two advantages over polymeric amines in interfacial composite membrane fabrication. First, monomeric amines can be obtained in most cases as pure crystalline compounds, identical in lot after lot. Polymeric amines, on the other hand, will show variations in purity, molecular weight, chain branching and viscosity from lot to lot. This adds an element of variability to the membrane fabrication process. Second, monomeric amines lead to thicker barrier layers, which consequently tend to show better abrasion resistance and greater tolerance to chemical attack. By contrast, a membrane such as PA-300 is normally overcoated with a protective layer of water-soluble polyvinyl alcohol to minimize abrasion and salt rejection losses during spiral element assembly. 

Aqueous Pb + undergoes loss of protons from bound water molecules with successive p/fg values of 7.8, 9.4, and 10.7 (at 0.16 ionic strength and 25 °C). Thus, at low total lead concentrations, both intracellular (pH 6.6) and extracellular (pH 7.4) body fluids contain mostly aquated Pb + with some aquated Pb(OH)+. Assuming that a similar pA a7.8 value prevails in Pb + complexes, an hydroxo complex may serve as a general base catalyst, a role that has been proposed several times. (Hydroxo complexes of metal ions may also serve as an effective hydroxide nucleophile. ) At the total concentrations of lead prevailing in many experiments, soluble polynuclear complexes form. First to appear at about 0.010 mM total lead is Pb3(OH)4 +, from pH 8 to 10. Greater total lead concentrations yield polynuclear species over the entire pH scale. 

A first patent for the technical implementation of ozonolysis of OA was claimed by Rieche [21]. According to a BASF patent filed in 1941, AA (97%) and PA (95%) are accessible by treatment of the ozonide with alkaline lye and Ag20 [22]. However, the technical manufacturing of AA succeeded first by Emery Industries in the year 1953 [23]. Their successor Emery Oleochemicals is still the worlds largest producer of AA by ozonolysis of OA with a production volume of about lOOOOt/year [9, 24]. The achievable yield of AA is 70-80% [24], based on the amount of applied OA. AA yields of more than 90% were obtained in a pilot plant [25]. The reaction is carried out in PA/water (70/30v/v) as solvent. The admixture of water reduces the formation of side products by removal of the heat of reaction via evaporative heat loss, and in addition, undesired reactive radicals are quenched by reaction with water [25, 26]. 

In general, one can select a dissipation factor or loss tangent derived from the ratio (G"IG ) or E"IE ) to represent the raiergy conversion pa- cycle. To a first approximation it is also possible to write... 

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