Page 121 - Interactive Theoritical Notes of Bioharmaceutics and pharamcokinetics.docx compressed

PharmD clinical pharmacy program Level 3, Semester 2 Biopharmaceutics & Pharmacokinetics (PT608(

(c)Drugs that are ionized over the entire pH range of the GIT

o The pH-partition hypothesis cannot explain the fact that certain drugs (e.g. quaternary

ammonium compounds and tetracyclines) are readily absorbed despite being ionized

over the entire pH range of the GIT.

▪ One suggestion for this is that the GI barrier is not completely impermeable to ionized

drugs.

▪ It is now generally accepted that ionized forms of drugs are absorbed in the small

intestine but at a much slower rate than the unionized form.

▪ Another possibility is that such drugs interact with endogenous organic ions of

opposite charge to form an absorbable neutral species - an ion pair - which is capable

of partitioning into the lipoidal GI barrier and be absorbed via passive diffusion.

(d) Lipid Solubility

✓ A number of drugs are poorly absorbed from the GIT despite the fact that their

unionized forms predominate.

✓ For example, the barbiturates, barbitone and thiopentone, have similar dissociation

constants - pKa 7.8 and 7.6, respectively - and therefore similar degrees of ionization

at intestinal pH.

✓ However, thiopentone is absorbed much better than barbitone.

✓ The reason for this difference is that the absorption of drugs is also affected by the

lipid solubility of the drug.

✓ Thiopentone, being more lipid soluble than barbitone, exhibits a greater affinity for

the GI membrane and is thus far better absorbed.

✓ An indication of the lipid solubility of a drug is given by its ability to partition

between a lipid-like solvent and water or an aqueous buffer.

120