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Vemgenterprise PDF
Vemgenterprise PDF
PRINCIPLES
1. THE LIVER IS THE MAJOR SITE OF METABOLISM FOR MANY DRUGS OR OTHER XENOBIOTICS.
OTHERS ORGANS: LUNGS, KIDNEYS AND ADRENAL GLANDS
2. MANY LIPID-SOLUBLE, WEAK ORGANIC ACIDS OR BASES ARE NOT READILY ELIMINATED FROM
BODY AND MUST BE CONJUGATED OR METABOLIZED TO COMPOUNDS THAT ARE MORE POLAR
AND LESS LIPID-SOLUBLE BEFORE BEING EXCRETED.
3. METABOLISM OFTEN RESULTS IN INACTIVATION OF THE COMPOUND.
4. SOME DRUGS ARE ACTIVATED BY METABOLISM. THESE SUBSTANCES ARE CALLED PRODRUGS.
BIOACTIVATION
ASPIRIN-
LOW DOSE→ FIRST
ORDER→T1/2=2-3 H
LARGE DOSE→URINE PH↓ →
REABSORPTION ↑ → ZERO
ORDER →T1/2=15-30 H
CLEARANCE (CL)
RELATES THE RATE OF ELIMINATION TO PLASMA
CONCENTRATION:
CLEARANCE= RATE OF ELIMINATION OF DRUG
PLASMA DRUG CONCENTRATION
(UNITS= VOLUME PER UNIT TIME)
HALF-LIFE OF DRUG (T ) 1/2
V = VOLUME OF DISTRIBUTION
D
CL = ELIMINATION CLEARANCE
E
C
ELIMINATED
t1/2
• STEADY-STATE CONCENTRATION (CSS)
• CONDITION IN WHICH THE AVERAGE TOTAL AMOUNT OF DRUG IN THE BODY DOES NOT CHANGE
OVER MULTIPLE DOSING INTERVALS
Drug Liver
duct
Biotransformation;
Hydrolysis by glucuronide produced
beta glucuronidase
gall bladder
Portal circulation
Gut
DRUG EVALUATION AND
REGULATION
THANK YOU!
• FDA RATINGS OF DRUG SAFETY IN PREGNANCY
•CATEGORY A
•ADEQUATE AND WELL-CONTROLLED STUDIES HAVE FAILED TO DEMONSTRATE A RISK TO THE
FETUS IN THE FIRST TRIMESTER OF PREGNANCY (AND THERE IS NO EVIDENCE OF RISK IN
LATER TRIMESTERS).
•CATEGORY B
•ANIMAL REPRODUCTION STUDIES HAVE FAILED TO DEMONSTRATE A RISK TO THE FETUS AND
THERE ARE NO ADEQUATE AND WELL-CONTROLLED STUDIES IN PREGNANT WOMEN.
•CATEGORY C
•ANIMAL REPRODUCTION STUDIES HAVE SHOWN AN ADVERSE EFFECT ON THE FETUS
AND THERE ARE NO ADEQUATE AND WELL-CONTROLLED STUDIES IN HUMANS, BUT
POTENTIAL BENEFITS MAY WARRANT USE OF THE DRUG IN PREGNANT WOMEN DESPITE
POTENTIAL RISKS.
• CATEGORY D
• THERE IS POSITIVE EVIDENCE OF HUMAN FETAL RISK BASED ON
ADVERSE REACTION DATA FROM INVESTIGATIONAL OR MARKETING
EXPERIENCE OR STUDIES IN HUMANS, BUT POTENTIAL BENEFITS MAY
WARRANT USE OF THE DRUG IN PREGNANT WOMEN DESPITE
POTENTIAL RISKS.
• CATEGORY X
• STUDIES IN ANIMALS OR HUMANS HAVE DEMONSTRATED FETAL
ABNORMALITIES AND/OR THERE IS POSITIVE EVIDENCE OF HUMAN
FETAL RISK BASED ON ADVERSE REACTION DATA FROM
INVESTIGATIONAL OR MARKETING EXPERIENCE, AND THE RISKS
INVOLVED IN USE OF THE DRUG IN PREGNANT WOMEN CLEARLY
OUTWEIGH POTENTIAL BENEFITS.