scholarly journals Titration Design: An Important Key in Drug Dose Determination

2019 ◽  
Vol 9 (4-s) ◽  
pp. 826-828
Author(s):  
Rada Santosh Kumar ◽  
R Venkata Sandhya
Keyword(s):  
Clinical Trials ◽  
Study Design ◽  
Dose Range ◽  
Drug Dose ◽  
Cumulative Effects ◽  
Optimum Dose ◽  
Response Relationship ◽  
Dose Response Relationship ◽  
Dose Determination ◽  
Type Study

Drug titration is the process of adjusting the dose of a medicine for the maximum benefits without adverse effects. To determine the optimum dose range the clinical trials are carried out and it is divided into two types of study design. The parallel type study design and titration type study design. The titration studies provide the information about the cumulative effects of the drug. Titration designs are mainly used in dose determining especially in insulin, anticonvulsants, anti-depressants, and sedatives. In the analysis of titration design, the phase I, II, III clinical trials are carried out to determine the dose-response relationship, safety and efficacy of the drug.

SENSITIVITY OF THE RAT TO INCREASING DOSES OF DEXTRAN

1962 ◽  
Vol 40 (6) ◽  
pp. 697-702 ◽  
Author(s):  
Gaetan Jasmin ◽  
Pierre Bois ◽  
Mai-Shian Su
Keyword(s):  
Toxic Effect ◽  
Intravenous Injection ◽  
Dose Response ◽  
Dose Range ◽  
Response Relationship ◽  
Dose Response Relationship ◽  
Toxic Dose ◽  
Lower Dose Range ◽  
Higher Doses ◽  
Adrenalectomized Rats

Increasing doses of dextran, a commercial 6% solution, were injected intravenously into both intact and adrenalectomized rats to evaluate the dose–response relationship. The minimum dose capable of producing an edema with 100% incidence was approximately 30 mg/kg in intact and only 4 mg/kg in adrenalectomized rats. Lower doses produced responses of decreasing intensity and incidence with a longer period of onset. Conversely, higher doses resulted in a shorter period of onset and a more intense reaction until a toxic dose was reached, beyond which cyanosis and shock appeared. Adrenalectomized rats reacted similarly to intact ones except that their response occurred at a lower dose range; they could not withstand the toxic effect of higher doses and died of circulatory failure. The fact reported by other workers that the edema is more intense and appears more rapidly after intravenous injection of minute rather than large quantities of dextran was not confirmed; the existence of a "critical dose" that does not produce any edema was not substantiated.

Fluoxetine seems to widen the nortriptyline antidepressant-like dose range in mice submitted to the tail suspension test (TST)

1992 ◽  
Vol 7 (1) ◽  
pp. 33-37
Author(s):  
IR de Oliveira ◽  
PR Brito ◽  
MF Peres ◽  
R Dardennes ◽  
MA da Rocha-Junior ◽  
...  
Keyword(s):  
Synergistic Effect ◽  
Dose Response ◽  
Dose Range ◽  
Tail Suspension Test ◽  
Response Relationship ◽  
Tail Suspension ◽  
Dose Response Relationship ◽  
High Doses ◽  
Higher Doses ◽  
Suspension Test

SummaryThis study was designed to verify whether fluoxetine (FL), a serotonin (5-HT) re-uptake inhibitor, would interfere with nortriptyline (NT), a biphasic U-shaped curvilinear dose-response relationship recently described in our laboratory. We associated 10 mg/kg NT or vehicle to 0, 5, 10, 20 and 40 mg/kg FL, in one group, and 10 mg FL or vehicle to 0, 5, 10, 20 and 40 mg/kg NT, in another group, 30 min before the tail suspension test (TST) in mice. Although we were not able to confirm a synergistic effect between FL and NT, FL-NT association seems to require higher doses of NT to block its own anti-immobility effect at high doses, thus widening NT effective antidepressant-like dose range in mice submitted to TST.

scholarly journals Dose–Response Relationship in Phase I Clinical Trials: A European Drug Development Network (EDDN) Collaboration Study

2014 ◽  
Vol 20 (22) ◽  
pp. 5663-5671 ◽  
Author(s):  
Victor Moreno García ◽  
David Olmos ◽  
Carlos Gomez-Roca ◽  
Philippe A. Cassier ◽  
Rafael Morales-Barrera ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Drug Development ◽  
Phase I ◽  
Dose Response ◽  
Response Relationship ◽  
Phase I Clinical Trials ◽  
Dose Response Relationship ◽  
Development Network

Dose-response relationship in phase I clinical trials: A European Drug Development Network (EDDN) collaboration study.

2011 ◽  
Vol 29 (15_suppl) ◽  
pp. 3084-3084 ◽  
Author(s):  
P. A. Cassier ◽  
V. Moreno Garcia ◽  
C. Gomez-Roca ◽  
D. Olmos ◽  
R. Morales ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Drug Development ◽  
Phase I ◽  
Dose Response ◽  
Response Relationship ◽  
Phase I Clinical Trials ◽  
Dose Response Relationship ◽  
Development Network

Comparative bio-assay of secretin and pancreozymin in rats and dogs

1962 ◽  
Vol 203 (5) ◽  
pp. 926-928 ◽  
Author(s):  
T. M. Lin ◽  
R. S. Alphin
Keyword(s):  
Enzyme Production ◽  
Dose Range ◽  
Relative Sensitivity ◽  
Volume Flow ◽  
Threshold Dose ◽  
Response Relationship ◽  
Dose Response Relationship ◽  
Conscious Rats ◽  
Relationship Of ◽  
Bio Assay

The dose-response relationship of secretin and volume flow and of pancreozymin and enzyme production was explored in the rat and dog. The relative sensitivity of the two species to the same secretin and pancreozymin preparations was compared. Anesthetics such as ether, chloroform, secobarbital, or pentobarbital sodium depressed the response of the rat to secretin. Linearity of response to secretin was observed in both rats and dogs; the range in the dog was 0.03– 0.5 mg/kg, whereas in the rat it was approximately 1.25–12.5 mg/kg. The threshold dose of secretin was the same for anesthetized and conscious rats, but the response of conscious rats to identical doses was much greater than that of anesthetized rats. A linear relationship between enzyme output and log dose of pancreozymin was found in both species; the dose range in the dog was from 2.5 to 1,000 µg, whereas in the rat the threshold dose was about 1 mg. Thus, the dog is more sensitive to both secretin and pancreozymin than the rat. Since results in the dog were easily reproducible, the dog is still the animal of choice for bio-assay of secretin and pancreozymin.

SENSITIVITY OF THE RAT TO INCREASING DOSES OF DEXTRAN

1962 ◽  
Vol 40 (1) ◽  
pp. 697-702 ◽  
Author(s):  
Gaetan Jasmin ◽  
Pierre Bois ◽  
Mai-Shian Su
Keyword(s):  
Toxic Effect ◽  
Intravenous Injection ◽  
Dose Response ◽  
Dose Range ◽  
Response Relationship ◽  
Dose Response Relationship ◽  
Toxic Dose ◽  
Lower Dose Range ◽  
Higher Doses ◽  
Adrenalectomized Rats

Increasing doses of dextran, a commercial 6% solution, were injected intravenously into both intact and adrenalectomized rats to evaluate the dose–response relationship. The minimum dose capable of producing an edema with 100% incidence was approximately 30 mg/kg in intact and only 4 mg/kg in adrenalectomized rats. Lower doses produced responses of decreasing intensity and incidence with a longer period of onset. Conversely, higher doses resulted in a shorter period of onset and a more intense reaction until a toxic dose was reached, beyond which cyanosis and shock appeared. Adrenalectomized rats reacted similarly to intact ones except that their response occurred at a lower dose range; they could not withstand the toxic effect of higher doses and died of circulatory failure. The fact reported by other workers that the edema is more intense and appears more rapidly after intravenous injection of minute rather than large quantities of dextran was not confirmed; the existence of a "critical dose" that does not produce any edema was not substantiated.

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