C. Cytotoxicity and Therapeutic Indexes
It is important to establish that an investigational drug has antiviral activity at concentrations that can be achieved in vivo without inducing toxic effects to cells. Furthermore, in a cell culture model, apparent antiviral activity of an investigational drug can be the result of host cell death after exposure to the drug. Cytotoxicity tests use a series of increasing concentrations of the antiviral drug to determine what concentration results in the death of 50 percent of the host cells (CC50 or CCIC50). The relative effectiveness of the investigational drug in inhibiting viral replication compared to inducing cell death is defined as the therapeutic or selectivity index (i.e., CC50 value/EC50 value). It is desirable to have a high therapeutic index giving maximum antiviral activity with minimal cell toxicity. We recommend determining CC50 values in both stationary and dividing cells from multiple relevant human cell types and tissues to ascertain the potential for cell-cycle, species, or tissue-specific toxicities. Studies determining cytotoxicity and therapeutic indexes should be conducted before the initiation of phase 1 clinical studies.
Source:
Drug Resistance Assay and Antiretroviral drug development guidance--->
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm071173.pdf
IV. NONCLINICAL STUDIES
A. Mechanism of Action
B. Antiviral Activity in Cell Culture
C. Cytotoxicity and Therapeutic Indexes
D. Protein Binding
E. Selection of Drug-Resistant HIV-1 Variants in Cell Culture
1. Genotype
2. Phenotype
F. Cross-Resistance
G. Characterization of Genotypic and Phenotypic Assays
1. Genotypic Assays
2. Phenotypic Assays
V. CLINICAL STUDIES: USE OF RESISTANCE TESTING IN CLINICAL PHASES OF DRUG DEVELOPMENT
A. General Considerations
B. Data Collection
C. Methods and Types of Analyses
1. Baseline Genotype and Virologic Response
2. Development of HIV Mutations
3. Baseline Phenotype and Virologic Response
4. Genotypic and Phenotypic Correlations: Changes in Susceptibility from Baseline
5. Cross-Resistance
6. Additional Analyses
D. Other Considerations
1. Role for Supporting Initial Activity and Dose-Finding Studies
2. Data Collection from Dose-Finding Trials
3. Use of Resistance Data to Establish an Indication
4. Use of Resistance Data for Study Enrollment Criteria, Background Regimen Selection, and Stratification Factors
5. Nonclade B Subtypes
E. Monitoring during Phase 4
REGULATORY REQUIREMENTS FOR SUBMITTING HIV RESISTANCE DATA
SUMMARY
There is much more information on HIV virus new findings available on this blog.
Here are given details about symptoms of AIDS , all new symptoms of AIDS and HIV virus infection are updated.
------------------------------------------------------------------------------------------------------------
This website provideds complete information about hiv virus , hiv infection , early hiv symptoms , hiv treatment,hiv test and hiv testing centers, aids symptoms, symptoms of hiv immideately after infection.------------------------------------------------------------------------------------------------------------
Following are the most read topic on this website you should find them on blog archive of this website
Stem cell treatment for AIDS
AIDS symptoms
SYMPTOMS OF HIV
HIV infection symptoms
Latest treatment for AIDS
How anti retroviral medicines are developed
How Chemotherapeutic drugs are developed to treat HIV virus infection
New drug developments against HIV Virus AIDS
Vaccines research for HIV AIDS Why it is difficult to develop a vaccine against HIV
Mother to child prevention of HIV virus infection.
hiv virus infection prevention and education bloggers
Last updated :28-Oct-2010
It is important to establish that an investigational drug has antiviral activity at concentrations that can be achieved in vivo without inducing toxic effects to cells. Furthermore, in a cell culture model, apparent antiviral activity of an investigational drug can be the result of host cell death after exposure to the drug. Cytotoxicity tests use a series of increasing concentrations of the antiviral drug to determine what concentration results in the death of 50 percent of the host cells (CC50 or CCIC50). The relative effectiveness of the investigational drug in inhibiting viral replication compared to inducing cell death is defined as the therapeutic or selectivity index (i.e., CC50 value/EC50 value). It is desirable to have a high therapeutic index giving maximum antiviral activity with minimal cell toxicity. We recommend determining CC50 values in both stationary and dividing cells from multiple relevant human cell types and tissues to ascertain the potential for cell-cycle, species, or tissue-specific toxicities. Studies determining cytotoxicity and therapeutic indexes should be conducted before the initiation of phase 1 clinical studies.
Source:
Drug Resistance Assay and Antiretroviral drug development guidance--->
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm071173.pdf
IV. NONCLINICAL STUDIES
A. Mechanism of Action
B. Antiviral Activity in Cell Culture
C. Cytotoxicity and Therapeutic Indexes
D. Protein Binding
E. Selection of Drug-Resistant HIV-1 Variants in Cell Culture
1. Genotype
2. Phenotype
F. Cross-Resistance
G. Characterization of Genotypic and Phenotypic Assays
1. Genotypic Assays
2. Phenotypic Assays
V. CLINICAL STUDIES: USE OF RESISTANCE TESTING IN CLINICAL PHASES OF DRUG DEVELOPMENT
A. General Considerations
B. Data Collection
C. Methods and Types of Analyses
1. Baseline Genotype and Virologic Response
2. Development of HIV Mutations
3. Baseline Phenotype and Virologic Response
4. Genotypic and Phenotypic Correlations: Changes in Susceptibility from Baseline
5. Cross-Resistance
6. Additional Analyses
D. Other Considerations
1. Role for Supporting Initial Activity and Dose-Finding Studies
2. Data Collection from Dose-Finding Trials
3. Use of Resistance Data to Establish an Indication
4. Use of Resistance Data for Study Enrollment Criteria, Background Regimen Selection, and Stratification Factors
5. Nonclade B Subtypes
E. Monitoring during Phase 4
REGULATORY REQUIREMENTS FOR SUBMITTING HIV RESISTANCE DATA
SUMMARY
There is much more information on HIV virus new findings available on this blog.
Here are given details about symptoms of AIDS , all new symptoms of AIDS and HIV virus infection are updated.
------------------------------------------------------------------------------------------------------------
This website provideds complete information about hiv virus , hiv infection , early hiv symptoms , hiv treatment,hiv test and hiv testing centers, aids symptoms, symptoms of hiv immideately after infection.------------------------------------------------------------------------------------------------------------
Following are the most read topic on this website you should find them on blog archive of this website
Stem cell treatment for AIDS
AIDS symptoms
SYMPTOMS OF HIV
HIV infection symptoms
Latest treatment for AIDS
How anti retroviral medicines are developed
How Chemotherapeutic drugs are developed to treat HIV virus infection
New drug developments against HIV Virus AIDS
Vaccines research for HIV AIDS Why it is difficult to develop a vaccine against HIV
Mother to child prevention of HIV virus infection.
hiv virus infection prevention and education bloggers
Last updated :28-Oct-2010
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