Time course of effect

Figure 6. Time course of effects of 10 ug chlorsulfuron per seedling on total phenolic content of sunflower hypocotyls expressed as -coumaric acid equivalents. Reproduced with permission from Ref. 75. Copyright 1983, J. Plant Growth Regul.

Pokora MJ, Richfield EK, Cory-Slechta DA. 1996. Preferential vulnerability of nucleus accumbens dopamine binding sites to low-level lead exposure time course of effects and interactions with chronic dopamine agonist treatments. JNeurochem 67 1540-1550. 

Relating the Time-Course of Plasma Concentrations to the Time-Course of Effect A critical decision to be made after the first human study is whether the compound s speed of onset and duration of action are likely to be consistent with the desired clinical response. Speed of onset is clearly of interest for treatments which are taken intermittently for symptoms rehef, for example, acute treatments for migraine, analgesics, or antihistamines for hay fever. Duration of action phase I is particularly important when the therapeutic effect needs to be sustained continuously, such as for anticonvulsants. The first information on the probable time course of action often comes from the plasma pharmacokinetic profile. However, it has become increasingly evident that the kinetic profile alone may be misleading, with the concentration-time and the effect-time curves being substantially different. Some reasons for this, with examples, include... 

Figure 6 Time course of effect of thloperamide on electrically-induced convulsions in mice. P < 0.05 and P < 0.01 vs. control group.

In terms of the time course of effects after longer naps, Lumley et al. (31) showed that increased alertness after 1- and 2-hr-long naps emerged 4 hours after napping and was maintained for at least 4 hr. Two-hour-long naps taken 6 or 18 hr into a 56-hr period of otherwise sustained wakefulness have been shown to produce performance improvements lasting at least 24 hr, while a 2-hr nap taken after 30 hrs awake improved performance for 8 hr (1). 

PHYSIOKINETICS — TIME COURSE OF EFFECTS DUE TO PHYSIOLOGICAL TURNOVER PROCESSES... 

Fink (279) supplied some Information about the time course of effects of WIN 2299. He gave 2.0-3.2 mg Intravenously and found that the subjects began to feel restless and excited by about 10 min after the Injection. These Initial effects might develop Into tense fearfulness with visual Illusions and delusions. Complaints of dryness of the mouth were elicited by questioning, but were not made spontaneously. The heart race did not change unless or until excitement and hyperactivity developed. The effects of these doses of WIN 2299 lasted for 2-3 h. 

An important assumption associated with the above-mentioned simple direct effect models is that a rapid equilibrium exists between plasma and effect site concentrations. Accordingly, maximum effects are predicted to occur simultaneously with peak drug concentrations. For many drugs, however, there is a temporal dissociation between the time course of concentration and the time course of effect, a phenomenon resulting in hysteresis observed in plots of effect vs. concentration as illustrated in Fig. 6. 

Pykko K. 1983. Time-course of effects of toluene on microsomal enzymes in rat liver, kidney and lung during and after inhalation exposure. Chem Biol Interact 44 299-310. 

George, S.G. and P. Young. The time course of effects of cadmium and 3-methylcholanthrene on activities of enzymes of xenobiotic metabolism and metallothionein levels in the plaice, Pleuronectes platessa. Comp. Biochem. Physiol. 83C 37—44, 1986. 

It is interesting to note that the transit model and the lifespan model both produce a very similar time course of effect if the transit model has sufficient (e.g., at least five) compartments. 

In comparison with phenytoin and carbamazepine, which induce changes in TGS of several hundred microampere, the effects of the fatty acids were rather small. However, a more conspicuous difference was the slow increase in threshold over a period of several hours. With intravenous administration of phenytoin, carbamazepine, or valproate, the maximal effect is reached almost immediately after injection, after which the threshold returns to baseline in 4—6 h. The pharmacokinetics were not investigated in detail, but the time-course of effect certainly did not follow the plasma concentration. Blood samples taken from some rats that were treated with DHA or EPA indicated that the plasma concentration was maximal at the end of the infusion and dropped to undetectable levels after 6 h (probably already after 3 h). 

Table 5-T Time Course of Effects of Nerve Agents 5-31, 31...

The time course of effect of these preparations is shown in Figure 41-2. 

Fig. 3. Time course of effect of Ap4A, ATP, or pyrophosphate on processing of poly(ADP-ribose) polymerase. Lymphocytes were treated with MNNG, permeabilized, incubated with [ P]NAD along with 10 mM Ap4A, ATP, or pyrophosphate for the indicated time periods. Products of each reaction were analyzed by SDS-polyacrylamide gel electrophoresis and autoradiography as discussed in Fig. 1 with quantitation performed as in Fig. 2. Control, PPi,OAp4A,- ATP...

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