Elimination curve

Drug elimination may not be first order at high doses due to saturation of the capacity of the elimination processes. When this occurs, a reduction in the slope of the elimination curve is observed since elimination is governed by the relationship Vmax/(Km- -[conc]), where Vmax is the maximal rate of elimination, Km is the concentration at which the process runs at half maximal speed, and [cone] is the concentration of the drug. However, once the concentration falls below saturating levels first-order kinetics prevail. Once the saturating levels of drugs fall to ones eliminated via first-order kinetics, the half time can be measured from the linear portion of the In pt versus time relationship. Most elimination processes can be estimated by a one compartment model. This compartment can... 

There was a significant negative correlation between (log) admission urinary PCP level and self-reported time since last PCP use (r= -0.53, p<0.001). Visual inspection of a graph of these two variables suggested a possible biphasic elimination curve, with the initial phase having a half-life of 5 to 7 days, and the later phase a half-life of about 30 days. However, formal curve fitting of these data to standard pharmacokinetic models (using BMDP... 

In rats, excretion of lead was biphasic following intravenous administration, with half-lives of 21 hours for the fast phase and 280 hours for the slow phase (Morgan et al. 1977). Dogs excreted lead in three phases, with half-lives of 12, 184, and 4,951 days (Lloyd et al. 1975). The half-life of the terminal phase of a biphasic elimination curve for mice was 110 days (Keller and Doherty 1980a). 

The answer is c. (Katzung, p 35.) The apparent Vd is defined as the volume of fluid into which a drug appears to distribute with a concentration equal to that of plasma, or the volume of fluid necessary to dissolve the drug and yield the same concentration as that found in plasma. By convention, the value of the plasma concentration at zero time is used In this problem, a hypothetical plasma concentration of the drug at zero time (7 mg/mL) can be estimated by extrapolating the linear portion of the elimination curve (the p phase) back to zero time. Therefore, the apparent is calculated by... 

FIGURE 3.2 Semilog plot of the plasma concentration, C, of a drug as a function of time, where Co is the projected plasma concentration at time zero and -1/2.303 is the slope of the elimination curve. 

The effect may wane faster than the plasma elimination curve due to tolerance, for example, benzodiazepines and nitrates. 

Quantitative estimation of ventilation by indirect methods in mussels requires four assumptions (16) a) reduction of concentration results from uptake, b) constant ventilation (pumping) rate, c) uptake of a constant percentage of concentration (first order process), d) homogeneity of the test solution at all times. Our transport studies have utilized antipy-rine (22, 23) a water soluble, stable chemical of low acute toxicity to mussels. It is readily dissolved in ocean water or Instant Ocean and is neither adsorbed nor volatilized from the 300 ml test system. Mussels pump throughout the 4 hour test period and this action is apparently sufficient to insure homogeneity of the solution. Inspection of early uptake and elimination curves (antipyrine concentration as a function of time) prompted use of Coughlan s equation (16) for water transport. 

Antipyrine from 300 ml solutions containing 0.6, 6, or 60pM was readily taken up by mussels. Within 40-80 minutes an apparent steady state was achieved. Uptake experiments were routinely conducted for 120 minutes (Figure 1). An analogous antipyrine elimination curve is shown in the lower portion of the figure. 

Estimated from linear portion of uptake and elimination curves (semilog). Six mussels per 300 ml containing 1.8 ymole antipyrine (0.6 pM). 

The half-life is the time it takes for the plasma drug concentration to decrease by 50%. Half-life is usually determined from the log-terminal phase of the elimination curve. However, it is important to remember that this parameter is a derived term and is dependent on the clearance and volume of distribution of the drug. Therefore, as CL and V change with disease, drug interactions, and age, so a change in the half-life should be expected. The half-life is typically calculated from the following equation ... 

In a case report of Wood et al. (2002) a 42-year-old man ingested an unknown quantity of stryehnine powder. Eight serum samples were taken over the first 5 days and analyzed subsequently for strychnine eoneentrations. The initial eoneentration at 1.5 h after ingestion was 4.73 mg/1, falling to 0.38 mg/1 at 74 h post-ingestion. Serum concentrations followed a monoexponential elimination curve with a ealculated elimination half-life of 12 h. The initial serum eoneentration of 4.73 mg/1 is the highest reported concentration in a patient who has survived. 

Butyric acid is rapidly metabolized in the liver to acetic acid and ketone bodies (acetone, acetoacetate, beta-hydroxybutyrate). In humans, the butyric acid elimination curve can be divided into two parts corresponding to two half-lives for the first (0.5 min), the slope suggests an accelerated excretion for the second (13.7min), a slow plateau is observed. 

Elimination. Elimination half-life indicates the rate of drug disappearance from plasma (and from brain) after distribution equilibrium has been reached and after the elimination curve has entered its terminal phase (also called the j3 phase). Clearance is the ratio of the rate of elimination over the arterial plasma concentration and would better describe the elimination process. However, it is more difficult to measure clearance than half-life therefore, half-life is used most often. 

The elimination rate always has units of (mass/ time) for any elimination process. For first-order processes, the elimination rate at any one moment is represented by a tangent to the elimination curve for any specified time t or drug concentration C. 

The elimination rate for zero-order processes may also be treated as a maximal rate of reaction (Fmax) and thus this type of data may be subject to ordinary Michaelis-Menten analysis (see further, below). Note that first-order elimination curves are so common that drug disappearance curves are routinely analyzed as semi-logarithmic plots (which linearizes the curve). The literature is sometimes ambiguous in its use of the term linear data , authors may or may not assume that the semi-logarithmic transformation is to be taken as read. 

W25. Winkler, K., and Gram, C., Models for description of bromsulfalein elimination curves in man after single intravenous injections. Acta Med. Scand. 169, 263-272 (1961). 

A) commercially coked up to 9.9% carbon. Curve B is the TPO of sample A after being burnt up to 723 K using programmed temperature. In this case, all the coke on the metal and a small part of the coke on the support were eliminated. Curve C shows the TPO of a catalyst sample coked in laboratory. The main difference between C and A is the larger amount of coke on the metal function of C because labo-... 

Further studies established that most alkyl mercurials pass through the bile and intestines and are reabsorbed (94). A logarithmic elimination curve which reaches background levels in 40 to 60 days (50) has been found with rats given single doses. Human volunteers excreted half in about 70 days (74, 95). The most active sites for mercury elimination are the kidneys, liver, hair, and feathers (95, 96, 97). In uncontaminated persons the kidneys have 20 times the concentration of the overall body average (95). Higher factors are found in persons exposed... 

After the regeneration step in air at 700°C, it is observed that all the coke present on the catalyst surface is eliminated (curve c). Furthermore, metallic nickel is converted into nickel oxide which has to be reduced before the subsequent reaction cycle. The average size of the NiO particles is estimated to be about 19.4 nm. 

The results are presented in Fig. 4. The clearance of injected histamine from the circulating blood was very rapid in the control session and oral administration of a high dose of oxatomide did not change the elimination curve. 

Knaak et al. ( ) detected parathion equivalents in low concentrations in blood soon after topical application. The parathion equivalents reached a maximum concentration within 12 hr as shown by the blood plasma absorption-elimination curve. These blood levels most likely occur in workers exposed to foliar residues of parathion and are responsible for illnesses reported in workers several hr... 

Thiodicarb was initially lost from skin at a rate similar to that of parathion and carbaryl. After 24 hr, the rate of loss decreased by a factor of 1/6. The initial loss of thiodicarb appears to be due to a combination of events which may include evaporative or other losses, the initial penetration of the dose into skin and rapid distribution to blood and other tissues. Absorption was slow after 24 hr as indicated by the t 1/2 for skin loss of 254 hr. Parathion and carbaryl, on the other hand, penetrated the skin and were absorbed at a more uniform rate after 24 hr according to the skin loss data. The plasma absorption-elimination curve for thiodicarb plateaued after 24 hr. The dose remaining on the surface of the skin acted as an infinite dose supplying the rat with a low but uniform amount of thiodicarb. 

Results for the various combinations of reverse current, field dropping to zero, and fixed field are shown in Fig. 2, and should be contrasted with the results of curves 1 and 2 of Fig. 2, where the holder was clamped securely. All the scatter in the data (Fig. 2) has been eliminated (curves 1 and 2) and, consequently, slight movements of the wire or of the holder must have been responsible for the scatter. The measurements recorded in curves 1 and 2 of Fig. 2 were repeated with the whole fixture immersed in frozen glycerin, and the results obtained were unchanged. 

Figure 4 shows a small selection of the results obtained using the apparatus of Figure 2. The points on the elimination curves are omitted for the sake of clarity. Reference 10 gives detailed results and a description of the experimental technique. Briefly, this was to hold a standard amount of lead, containing about 0.05% Cu, plus other elements as required, at a constant temperature, and to stir in the reagent (sulfur or sulfiir/pyrites mixture).

Figure 10 - Zinc Elimination Curves - One Showing Effect of Correction Temperature 560 C L = 30 cm, Various Vacua, Cold Condenser, CC, or Liquid Zinc Condenser, LZ, at Zinc Melting Point, 420° C, See Text and Reference 2...

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