Steady-state concentration, time reach

Aripiprazole has been approved for treatment of schizophrenia and acute manic or mixed episodes in bipolar disorder. This medication is also indicated for maintenance treatment in bipolar I disorder. The recommended starting and target dose for aripiprazole in patients with schizophrenia is 10 or 15 mg/day. This is a once-daily dose, and patients can take the medication with or without food. Although this medication has been shown to be effective in doses ranging from 10 to 30 mg/day, doses higher than 10-15 mg have not been shown to be more effective than 10- to 15-mg doses in patients with schizophrenia. The recommended starting dose for treatment of an acute manic or mixed episode is 30 mg the recommended dose for maintenance treatment in stable patients is 15 mg/day. The elimination half-life is 75 hours, and steady-state concentrations are reached within 2 weeks. Therefore, dose adjustments are recommended every 2 weeks, to allow time for clinical assessments of the medication s effects to be observed at steady-state concentration. Peak plasma concentrations occur within 3-5 hours. At equivalent doses, the plasma concentrations of aripiprazole from the solution were higher compared with plasma concentrations associated with the tablet form. 

The time course of drug accumulation and elimination. Solid line Plasma concentrations reflecting drug accumulation during a constant rate infusion of a drug. Fifty percent of the steady-state concentration is reached after one half-life, 75% after two half-lives, and over... 

Figure 1 shows a typical curve obtained for most photochromic systems. In the dark, there should be no absorbance by the colored form of the photochrome. At time, ti, the exciting radiation is turned on which immediately causes conversion of the initial molecule, X, into its colored form Y. The absorbance of Y builds up to a maximum value with time until a steady-state concentration is reached in the reaction, X Y. When the exciting radiation is shut off, the colored form Y reverts to X at a rate dependent on the kinetics of the dark reactions. 

Steady state concentrations were reached during the exposure experiments reported here since the time of wetness per cycle was 420 min and the residence time was 112 min. An expression for the... 

Pioglitazone is available in 15-, 30-, and 45-mg tablets. When administered in the fasting state, pioglitazone is measnrable in sernm within 30 min and peak concentrations occnr in 2 h [27], Administration of pioglitazone with food delays the time to peak concentration to 3 h bnt does not diminish the extent of its absorption. Pioglitazone alone has a half-life of 3-7 h pioglitazone in combination with its active metabolites has a half-life of 16-24 h. Steady-state concentrations are reached within 7 days. Its volnme of distribntion is... 

Hydrocodone has a half-life of 3.8 boms, peak effect at 1.3 hours, and a duration of 4.6 hours. It is metabolized by the liver and excreted primarily in urine. Hydrocodone is oxidized to hydromorphone by cytochrome P450 2D6. The extended-release formulation has measurably different pharmacokinetics following a single dose of 1,2 or 3 HC/ APAP CR tablet(s), the mean maximum plasma concentration (C ) ranged from 13.3 to 36.8 ng/mL for HC and 2.01 to 6.68 ng/mL for APAP. The mean time to reach (T ) was 6.0-6.7 hours for HC and 1.1-1.3 hours for APAP. Following twice-daily dosing of 2 HC/APAP CR tablets for 3 days, steady-state HC/APAP concentrations were attained by 24 hours [3,4]. The mean on day 3 was 37.0 ng/mL for HC and 4.96 ng/mL for APAP. Systemic exposures of HC and APAP demonstrated a dose-proportional increase from one to three tablets. Steady-state concentrations were reached by 24 hours with minimal accumulation following twice-daily administration. Thus, it can be taken every 12 hours [4]. 

Chromium plating from hexavalent baths is carried out with insoluble lead-lead peroxide anodes, since chromium anodes would be insoluble (passive). There are three main anode reactions oxidation of water, reoxidation of Cr ions (or more probably complex polychromate compounds) produced at the cathode and gradual thickening of the PbOj film. The anode current density must balance the reduction and reoxidation of trivalent chromium so that the concentration reaches a steady state. From time to time the PbOj film is removed as it increases electrical resistance. 

The interpretation of the above data on iodination has been questioned by Buss and Taylor217, and by Grovenstein et a/.218,219. The former workers studied the iodination of 2,4-dichlorophenol at about 25 °C using a stirred flow reactor, the advantages of which are that once a steady state has been reached there is no change in the concentration of the reactive species in the reactor with time and the rate of reaction is simply a product of extent of reaction multiplied by the reciprocal ol the contact time hence it is possible to use unbuffered solutions and low iodide ion concentrations. They found general catalysis by the base component of added phosphate buffers and the observed rate coefficients varied with [H+ ] according to... 

A practically unlimited source of plutonium was present, so that its concentration in solution (dissolved or otherwise dispersed) could, at least in theory, increase continuously with time until a steady-state situation was reached. 

Continuous Polymerizations As previously mentioned, fifteen continuous polymerizations in the tubular reactor were performed at different flow rates (i.e. (Nj g) ) with twelve runs using identical formulations and three runs having different emulsifier and initiator concentrations. A summary of the experimental runs is presented in Table IV and the styrene conversion vs reaction time data are presented graphically in Figures 7 to 9. It is important to note that the measurements of pressure and temperature profiles, flow rate and the latex properties indicated that steady state operation was reached after a period corresponding to twice the residence time in the tubular reactor. This agrees with Ghosh s results ). 

Because ATP hydrolysis on F-actin takes place with a delay following the incorporation of ATP-subunits, and because in the transient F-ATP state filaments are more stable than in the final F-ADP state, polymerization under conditions of sonication can be complete, within a time short enough for practically all subunits of the filaments to be F-ATP. At a later stage, as Pj is liberated, the F-ADP filament becomes less stable and loses ADP-subunits steadily. The G-ADP-actin liberated in solution is not immediately converted into easily polymerizable G-ATP-actin, because nucleotide exchange on G-actin is relatively slow, and is not able to polymerize by itself unless a high concentration (the critical concentration of ADP-actin) is reached. Therefore, G-ADP-actin accumulates in solution. A steady-state concentration of G-ADP-actin is established when the rate of depolymerization of ADP-actin (k [F]) is equal to the sum of the rates of disappearance of G-ADP-actin via nucleotide exchange and association to filament ends. [G-ADP]ss in this scheme is described by the following equation (Pantaloni et al., 1984) ... 

Continue to monitor AED serum trough concentrations approximately every 3 to 5 days until the AEDs have reached steady-state concentrations. Give additional loading doses or hold doses as needed to maintain trough concentrations in the patient s therapeutic range. Be sure to evaluate the time the sample was drawn to assure it is a trough level. 

Consider a tube of length / containing a solution of concentration c2, with one end (jc = 0) rinsed with a solution of concentration cx and the other (jc = /) with a solution of concentration c2. In contrast to the previous example, after a period of time steady state will be reached, characterized by the relationship... 

Improvement in symptoms and laboratory abnormalities should occur within 4 to 8 weeks, at which time a tapering regimen to maintenance doses can be started. Dosage changes should be made on a monthly basis because the endogenously produced T4 will reach a new steady-state concentration in this interval. Typical daily maintenance doses are PTU 50 to 300 mg and MMI 5 to 30 mg. 

Mathematically, steady-state is never reached within a finite time. For practical purposes, however, one can compute the time necessary to reach steady-state by imposing the condition that a given transient magnitude (concentration or flux) differs from the steady-state value in a reasonably low relative proportion [42], For calculating the proximity to steady-state, the diffusive flux Jm is more convenient than the internalisation flux /u, because of the continuously decreasing behaviour with time of the former. 

When an enzyme is mixed with a large excess of substrate (which is generally the case due to the high catalytic efficiency of enzymes), there is an initial period, the pre-steady state period, during which the concentrations of enzyme bound intermediates build up to their steady state levels. Once the intermediates reach their steady state concentrations (and this is generally achieved after milliseconds) the reaction rate changes only slowly with time. 

Also bioaccumulating substances may in some situations call for a higher assessment factor. If accumulation is likely, the toxicity studies need to be of sufficient length to cover the accumulation period (e.g., the time to reach a steady-state concentration). If there is limited information on these aspects, it has to be considered to which extent this lack of information should affect the assessment factor. 

Easterby proposed a generalized theory of the transition time for sequential enzyme reactions where the steady-state production of product is preceded by a lag period or transition time during which the intermediates of the sequence are accumulating. He found that if a steady state is eventually reached, the magnitude of this lag may be calculated, even when the differentiation equations describing the process have no analytical solution. The calculation may be made for simple systems in which the enzymes obey Michaehs-Menten kinetics or for more complex pathways in which intermediates act as modifiers of the enzymes. The transition time associated with each intermediate in the sequence is given by the ratio of the appropriate steady-state intermediate concentration to the steady-state flux. The theory is also applicable to the transition between steady states produced by flux changes. Apphcation of the theory to coupled enzyme assays makes it possible to define the minimum requirements for successful operation of a coupled assay. The theory can be extended to deal with sequences in which the enzyme concentration exceeds substrate concentration. 

Ribavirin can be administered as an aerosol using a small-particle aerosol generator. When administered by this route, the drug has only minimal systemic absorption, with drug concentrations in respiratory tract secretions approximately 100 times as high as those found in plasma. Oral absorption is rapid, and first-pass metabolism is extensive ribavirin s oral bioavailability is 64% and can be increased by administration with a high-fat meal. Steady-state levels are reached after 4 weeks. 

Steady state may be reached in a diffusion problem proceeding for a long time in a finite medium. Steady state means that the concentration at any point does not change with time any more, i.e.,... 

The time required for achieving the steady-state concentration depends on the value of Cq and the precision required. Take the required precision to be 1% relative. If Cq < pa /D, then the condition of t —> oo is roughly satisfied when Dtja > 2. If Co > pg /(3D), then steady state is reached when Df/g is greater than (4/7i )ln[100 8Q/7i —96/ti ], where Q=Co/[pg /(3D)]. The steady-state volume-average concentration corresponds to a steady-state apparent age of... 

By setting the input function, I(t), in the differential equations on p. 28 to a constant rather than zero the equations can be solved to yield the disposition function for an intravenous infusion. With a fixed rate infusion, the plasma concentration will gradually increase towards a steady state concentration, CSS. Since CSS is constant, the amount of drug entering the body via the infusion at steady state must equal that being eliminated, (i.e. the clearance). Thus the infusion rate, R, e.g. mg min-1, needed to reach CSS is R=CSS.CI. It will take approximately 4 to 5 terminal half-lives to reach 95% CSS. Note that if the infusion rate is doubled CSS will also double, but the time taken to reach CSS remains the same, i.e. it is independent of the infusion rate (Figure 2.6). 

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