Onset time

Delayed action soHd products are designed like conventional dosage forms to release all their dmg contents at one time, but only after a delayed period. Thus, the duration of action and the blood concentration—time curve is like that of a conventional product. However, the onset time is purposely designed to be long. 

Intravenous aqueous injections provide an excellent means of achieving a rapid therapeutic response. Parenteral product design, eg, vehicle and other excipient selection, as well as choice of route of adrninistration, can prolong therapeutic activity and increase onset times. Thus, oily solutions, suspensions, or emulsions can be adrninistered by subcutaneous or intramuscular routes to create prolonged effect, ie, depot injection (28). 

Fig. 46.—Schematic Effect of Concentration of Persistence Time (Tp), Subjective Intensity (Si), and Onset Time (Tp) of Sucrose Sweeteners. ...

Cho A-H, Lee DH, Kim JS, Choong GC, Kwon SU, Suh DC, Choi J, Chun S-B, Kim SJ, Kang D-W. MRI-Based thrombolysis in acute stroke patients with unclear onset time is safe and feasible Stroke 2006 37 634 (abstract, American Stroke Association International Stroke Conference 2006). 

Acute stroke is considered to be an acute medical emergency. Identification of the time and manner of stroke onset is an important determinant in treatment. The time the patient was last without symptoms is used as the time of stroke onset. Since patients typically do not experience pain, determining the onset time can be difficult. It is also important to document risk factors and previous functional status of the patient to assess current disability due to the stroke. 

In contrast, another meta-analysis undertaken by Brzezinski et al., using 17 different studies involving 284 subjects, most of whom were older, concluded that melatonin is effective in increasing sleep efficiency and reducing sleep onset time (Brzezinski et al. 2005). Based on this meta-analysis the use of melatonin in the treatment of insomnia, particularly in aged individuals with nocturnal melatonin deficiency, was proposed. 

A number of clinical studies have now made use of the phase advancing property of melatonin for treating delayed sleep phase syndrome (DSPS). Melatonin, at a 5 mg dose, has been found beneficial in advancing the sleep onset time and wake time in DSPS subjects (Dahlitz et al. 1991 Nagtegaal et al. 1998 Kayumov et al. 2001). Melatonin was found to be effective when given five hours before its endogenous onset or seven hours before sleep onset. 

LY 156735 is a [1-substituted analog of melatonin that has greater bioavailability than melatonin (Nickelsen et al. 2002). It is in an earlier stage of clinical trials in initial trials, it reduced the sleep onset time in patients with moderate sleep-onset insomnia. Several other specific melatonin receptor agonists and antagonists are in development (Rivara et al. 2005 Zlotos 2005) and presumably will be clinically tested over the next few years. 

Ixiqu t) = Ix(L2) was zero up to ri(OM) and it starts increasing after ti(OM). This is very different to Ix(qvbt). This suggests that the lamellar stacking is not superimposed during the induction period. The onset time of lamellar stacking ronset(L) is estimated as,... 

Lamellae start stacking much later than nuclei start developing. The onset time of stacked lamellae was similar to the induction time. Therefore, nucleation during the induction period can be observed without being affected by the stacked lamellae. 

Future developments will include the development of consensus parameters that describe realistic medical countermeasure effects. An important new feature will consist in the assessment of casualty flow onset times, by calculating the dose-build-up and the resulting development of casualty probabilities in time. 

Onset Time of Symptoms Symptoms appear much more slowly from skin dosage than from respiratory dosage. Although skin absorption great enough to cause death may occur in 1 to 2 minutes, death may be delayed for 1 to 2 hours. Respiratory lethal dosages kill in 1 to 10 minutes, and liquid in the eye kills almost as rapidly. 

Onset time (Tonso) - Time at which the first of two successive NF scores below 25% of baseline occurs in subjects who subsequently become incapacitated. 

Dose-Onset factor (Donset) - the factor by which onset time (Tonso) is shortened by administering twice the incapacitating dose. 

Note that, to call attention to an important source of variability in the onset time, we used the term dose onset factor (Donset). As stated, it represents the decrease in Tonso, (the time at which NF performance first falls below 25% of baseline) when the incapacitating dose (IDso) is doubled. In the case of BZ, for example, doubling the absorbed dose shortens the Tonso from four hours to less than an hour. Doubling it again presumably shortens it to just a few minutes. This would be an important concept for military plarmers to consider. Our data were insufficient to measure the Domet precisely because we preferred not to administer double doses to volunteers, hr the few cases in which actual aerosol doses were considerably higher than the intended value, however, the dramatically earlier onset of incapacitation allowed an educated guess of the Donset. 

In actual use, many among the target population would necessarily receive multiples of the IDso and be unable to function within a few minutes. This would create both an early and dramatic psychological impact as well as a rapid effect on performance. BZ and similar belladonnoids would actually begin to cause casualties in a very short time. Unfortunately, because the official onset time is about four hours, the markedly more rapid onset of incapacitation at higher doses can easily be overlooked or ignored by military planners. 

The second glycolate chosen for thorough evaluation was EA 3443 (Fig. 15). It proved to have characteristics very similar to BZ with an almost identical onset time and duration ". It was at least 50% more potent, however, and had greater relative central potency. Our studies of EA 3443 were more systematic than those we had done with BZ. We had the advantage of more than a year of protocol development - a gradual process that became more sophisticated as experience with BZ increased. 

Agent ID50 (i.v. or im) meg/kg ID 50 (i.v. or. i.m) meg/kg ICtso Mg min/ cubic M Onset Time Tonso (h) Partial Recovery Time Toffso (h) Duration of Severe effects Dsofh) Prolong ation-Time (h) Relative Central Potency Safety Factor... 

By inspection, atropine s effects on cognitive (NF) performance reach a maximum at about 4 hours (Fig. 60). The estimated MED50 is about 90 mcg/kg and the ID50 is about 160 mcg/kg. Onset time (Tonso) and duration (D50) at the IDso.are about 1 and 6 hours respectively. The relative central potency of atropine is the lowest of any of the belladonnoids we studied (Fig. 74). Once again, as is the case with BZ vs. EA 3167 and EA 3443 vs. EA 3580, a minor structural change makes a major difference. 

Onset time (Ton5o) at the ID50 is about 30 minutes. Partial recovery time (75% of baseline) is about 7 hours and full recovery occurs at about 10 hours. 

Welgaod and Mershon22 tested 39 subjects for skin reactions to CR, using 1-cm2 patches soaked with CR-propylene glycol solutions. Each patch was wetted with 0.1 ml of 0.01, 0.05, 0.10, 0.25, 0.50, or 1.0X CR, Ezposure times were 5 and 30 min, and tests were made at 18.3 and 25.6°C. The concentration of CR did not affect the time of onset of sensation higher temperature decreased onset times. Subjects differed widely, both In time of onset and termination of Irritation and In reported Intensity of sensation. Intensity was not related to concentration of CR, ezposure time, or temperature. The degree of erythema was variable, but It disappeared In 2-4 h. All CR concentrations were judged to be relatively harmless. 

Pharmacokinetics is the study, which determines the rapidity and concentration of the drug in the body and its duration of appearance at the target organ, i.e. onset, time of peak action and duration of action and by these also determine the route(s) and frequency of administration of drug. 

Zaleplon s onset time, time to maximal drug effect, and duration of action are shorter than with triazolam. Hence, despite its non-BZD structure and unique BZD receptor binding profile, its behavioral pharmacological profile is similar to that of triazolam ( 157). Like zolpidem, zaleplon in recommended doses decreases sleep latency with minimal effect on sleep stages. Thus, it differs from BZDs, which prolong the first two stages of sleep and shorten stages 3 and 4 REM sleep ( 158). 

---