Bioavailability

Question 1

Bioavailability

Answer 1

• Rate and extent to which all active ingredient or therapeutic moiety is absorbed from a product and becomes available at site of action
• Two types: Absolute and relative

Question 2

AUC Calculations

Answer 2

• Used to measure bioavailability
• Estimation technique: Trapezoidal Method
• Also Absolute and relative calculations

Question 3

Absolute Bioavailability

Answer 3

• AUC0-INF, more accurate than AUC form 0 to last time period measured
• Extravascular
• IV bolus

F = (AUC0-INF)oral/(AUC0-INF)iv X (Dose)iv/(Dose)oral

AUC from the last time period measured to infinity = Clast/Kel (Kel = elimination rate)

-Add that answer to AUC0-last time period measured to get a more accurate AUC and bioavailability overall

Question 4

Relative Bioavailability

Answer 4

• Comparative Bioavailability
• Plasma or urine can be used
• Compares two different dosage forms

Plasma: F = same as absolute bio. except with whatever two dosage forms are being compared

Urine: (Xu)tablet/(Xu)im X (Dose)im/(Dose)tablet

Question 5

Bioequivalence

Answer 5

• Comparison of AUC0-INF, Cmax, and Tmax
• Compares pharmaceutically equivalent products
• Brand (Innovator) v.s. Generic

F = same as before but with brand and generic rather than different dosage forms or IV v.s. Oral

Question 6

Statistical Analysis Requirements

Answer 6

• Two one-sided tests procedure
• Test(T) is not significantly less than reference by 20%
• Reference(R) is not significantly less than test by 20%

R/T = 80/100 = 80%
T/R = 100/80 = 125%
Range of 80-125% of difference allowed by FDA