Single dose curve

FIGURE 11.4 Two-way analysis of variance. Arrangement of data in rows and columns such that each row of the cell culture plate (shown at the top of the figure) defines a single dose-response curve to the agonist. Also, data is arranged by plate in that each plate defines eight dose-response curves and the total data set is comprised of 32 dose-response curves. The possible effect of location with respect to row on the plate and/or which plate (order of plate analysis) can be tested with the two-way analysis of variance. 

FIGURE 11.16 Control dose-response curve and curve obtained in the presence of a low concentration of antagonist. Panel a data points. Panel b data fit to a single dose-response curve. SSqs = 0.0377. Panel c data fit to two parallel dose-response curves of common maximum. SSqc = 0.0172. Calculation of F indicates that a statistically significant improvement in the fit was obtained by using the complex model (two curves F = 4.17, df=7, 9). Therefore, the data indicate that the antagonist had an effect at this concentration. 

TED50= Tl[2 (IM/H) ln(2 + (Cpeak/CE50) AH) TED90 = 7T/2 (IM/H) ln(10+9 (Cpeak/CE50)A//) For single dose monoexponential kinetics and direct effect conditions, the area under the effect time curve (AUEC) can be derived by integration of the Hill equation. 

The effect of incomplete absorption is that only a fraction of a single-dose D is made available to the central plasma compartment. The solution of the previous model needs, therefore, to be modified by replacing the term D by F D. Consequently the area under the curve AUCg under incomplete extravascular absorption will be smaller than the maximal AUC that results from complete absorption. The latter, as we have seen is equal to the AUC obtained from a single intravenous injection, which we denote by AUC,. These considerations can be summarized as follows ... 

When a single-dose intravenous and an oral (or other extravascular) plasma curve are both available from the same subject(s) one can define the mean absorption time MAT by means of the mean residence time obtained from the intravenous curve MRT, and the extravascular curve MRT ... 

Daneshmend [104] measured the serum concentration of miconazole in 11 healthy adult females for 72 h following a single 1200 mg vaginal pessary. The mean peak serum miconazole concentration was 10.4 pg/L and the mean elimination half-life was 56.8 h. The mean area under the serum concentration-time curve was 967 pg/L/h. The calculated mean systemic bioavailability of the vaginal pessary was 1.4%. There was large intersubject variation in serum miconazole pharmacokinetics. This formulation may provide effective single dose treatment for vaginal candidiasis. 

Figure 3 Rodent pharmacodynamic effects versus CbjU for 6. Dashed lines represent a twofold separation from the in vitro functional assay EC50 (122 nM, dashed arrow). mSLA, mouse spontaneous locomotor activity mPPI, mouse prepulse inhibition DRC, dose-response curve SD, single dose. (See Color Plate 4.3 in the Color Plate Section.)...

Many methods exist for representing the response-dose curve.1 For single exposures the probit (probit <= probability unit) method is particularly suited, providing a straight-line equivalent to the response-dose curve. The probit variable Y is related to the probability P by2... 

Toxicants are compared for relative toxicity based on the LD, ED, or TD curves. If the response-dose curve for chemical A is to the right of the response-dose curve for chemical B, then chemical A is more toxic. Care must be taken when comparing two response-dose curves when partial data are available. If the slopes of the curves differ substantially, the situation shown in Figure 2-13 might occur. If only a single data point is available in the upper part of the curves, it might appear that chemical A is always more toxic than chemical B. The complete data show that chemical B is more toxic at lower doses. 

It is necessary to determine the toxicity of a drug. The maximum tolerable dose and area under the curve are established in rodents and nonrodents. There are two types of toxicity studies single dose and repeated dose. Single... 

Currently approved NRT products include the transdermal nicotine patch and several acute NRT products, including nicotine gum, lozenge, sublingual tablet, vapor inhaler, and nasal spray. The single-dose nicotine plasma curves for transdermal patch, gum, nasal spray, lozenge, as well oral snuff and a cigarette, are illustrated in Fig. 1 (note for the sake of simphcity, the curve for sublingual tablet is not illustrated, but because of the route of nicotine delivery, the plasma curve is qualitatively similar to nicotine gum). 

In vitro clonal tumor cell studies have demonstrated the severe cytotoxicity of a-particles delivered by At single exponential cell survival-dose curves were obtained, with (37% survival) values of 29-48 cGy and 57-73 cGy for Chinese hamster V-79 (5J ) and HEp2 cells, respectively (55). In both studies the oxygen enhancement ratio (OER) was found to be slightly greater than unity, probably resulting from the low-LET components of At decay (see Fig. 5). In biological systems, such a-particle emissions enable comparable cytotoxicities to be effected in both hypoxic and euoxic tumor cell populations. 

When mmor data are used, a POD is obtained from the modeled mmor incidences. Response levels at or below 10% can often be used as the POD. The POD alone, being a single-point estimate of a single dose-response curve, does not convey all the critical information present in the data from which it is derived. To convey a measure of uncertainty, the POD should be presented as a central estimate with upper and lower bounds. The POD for extrapolating the relationship to environmental exposure levels of interest, when the latter are outside the range of observed data. 

The dose distribution in the materials is given as a depth-dose curve. An example of the curve is illustrated in Fig. 4 obtained with the irradiation of electron from 0.5 to 1.0 MeV using cellulose triacetate (CTA) film dosimeter [12]. The existence of the maximum dose is an important characteristic of the depth-dose curve. Irradiation from two opposite sides by using two accelerators was proposed in order to give better uniformity in water [13]. The uniform irradiation is also important for flue gas treatment. Better efficiency of NO removal was proved with both-side irradiation by using three accelerators for coal-fired flue gas than single-side irradiation at the same dose [14]. 

Figure 14 Proton beam irradiation of a deep-seated large tumor. Single Bragg peaks of different energy are combined, in adequate proportions, to obtain a homogeneous dose distribution at the level of the SOBP. The depth-dose curve of a photon beam, shown for comparison, is inferior compared to the proton curve. However, an optimized multifield photon treatment allows to reach better irradiation conditions. (From Ref 43.)...

Pharmacokinetics Complete and consistent blocking of the IL-2 receptor is maintained as long as serum basiliximab levels exceed 0.2pg/ml. As concentrations fall below this level, expression of IL-2 receptor returns to pre-therapy values within 1-2 weeks. Basiliximab has a steady-state volume of distribution of 9 liters and total body clearance of 41 ml/h. Its elimination half-life ranges from 7 to 10 days. There is a dose-proportional increase in peak concentration (Cmax) and area under the curve (AUC) up to the highest tested single dose of 60 mg. No clinically relevant influence of body weight or gender on distribution volume or clearance has been observed in adult patients. Elimination... 

Pharmacokinetics Following single doses of Remicade up to 20 mg/kg, maximum drug concentration and area under the curve (AUC) were proportional... 

FIG. 3-1. Single-dose plasma drug concentration versus time curves for the same dose of the same drug given to the same individual by three different routes. (From Janicak PG, Davis JM. Pharmacokinetics and drug interactions. In Sadock BJ, Sadock V, eds. Kaplan Sadock s comprehensive textbook of psychiatry, Vol. 2, 7th ed. Philadelphia Lippincott Williams Wilkins, 2000 2251, with permission. Artwork created by Matthew Janicak.)... 

There are other clinically important parameters beyond the extent of absorption that are apparent on the single-dose plasma curve. These include the following ... 

Area under curve (AUC] The total area under the plot-of-drug concentration versus time following either a single dose or multiple doses of a specific drug product (e.g., formulation) in a specific patient by a specific route of administration. 

Target area under the concentration time curve after a single dose. 4... 

To assess the potential for an interaction between raloxifene and warfarin, 15 healthy postmenopausal women each received single doses of warfarin 20 mg before and during 2 weeks of dosing with raloxifene 120 mg/day (37). Raloxifene reduced the oral clearance of R- and A -war-farin respectively by 7.1 and 14% and the oral volume of distribution by 7.4 and 9.8%. Raloxifene reduced the maximum prothrombin time by 10% and the area under the prothrombin versus time curve from 0-120 hours by an average of 8%. The authors concluded that raloxifene may produce a small increase in systemic warfarin exposure but a reduced pharmacodynamic effect. Since the effects are slight this interaction is unlikely to have clinical consequences. 

Middle two curves (rat 100). Effect of a single dose of angiotonin. At A.O. amine oxidase was injected, which returned the moderately elevated blood pressure to control values. After 5 minutes the same dose of angiotonin was given, with a modified response. Rat was normotensive. 

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