3.1 A drug has a log D60 value of 3.7 and is poorly soluble in aqueous media. Wh

Question

3.1 A drug has a log D60 value of 3.7 and is poorly soluble in aqueous media. When administered orally, approximately 30% of a dose is lost due to incomplete dissolu- tion. It encounters no further problems during absorption, but it is a CYP3A4 sub- strate, and about 25% of the drug passing through the membrane undergoes intestinal metabolism. During its initial pass through the liver, about 70% of the drug is lost due to metabolism. (a) Calculate Fa Fg, Fh and F for this drug. (b) Determine the effective dose when 50 mg is given orally. (c) Determine the value of an intravenous dose that is equivalent to a 100-mg oral dose.

Explanation / Answer

(a) F = Fa × Fg × Th

Fa=fraction of dose absorbed; 70% of 100=70%(assume, initial=100)

Fg=fraction of drug passing through membrane without metabolism; 75% of 70= 52.5%

Fh=fraction of drug passing through liver without metabolism and biliary excretion; 30% of 52.5= 15.75%

Therefore, F = 70/100×525/1000×1575/10000 = 0.0578 = 5.78%

(b) Bioavailability = F%

Effective Dose(ED) for 50mg = 5.78/100 × 50 = 2.89mg.

(c) IV dose will be equivalent to F% of orally administered dose.

F% of 100mg = 5.78/100 × 100 = 5.78mg.

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