Page 182 - Medicinal Chemistry Self Assessment

2.15 Fluvoxamine 171

Answer
Maleate salts are water soluble organic salts. Water soluble organic salts generally enhance overall
drug water solubility (see Chapter 5 in Basic Concepts in Medicinal Chemistry). Maleate salts typically
demonstrate enhanced solvation and dissolution as compared to their free base forms. This is excep-
tionally beneficial in the preparation of parenteral, nasal, and ophthalmic dosage forms where the
delivery of small volumes of highly concentrated solutions is necessary.

4. Fluvoxamine is well absorbed and has an oral bioavailability of ~50%. Using the information found in
the structure evaluation grid, provide a rationale for these pharmacokinetic properties.

Answer
Orally administered drugs must strike a balance between having enough hydrophilic character to
promote dissolution and solubility in the aqueous contents of the gastrointestinal (GI) tract, and
sufficient hydrophobic character to allow for absorption across the lipid bilayer membrane. Fluvox-
amine has a fluorinated aliphatic alkane, an ether, and an ionized primary amine that contribute
to the overall hydrophilic character of the drug. An aromatic hydrocarbon and aliphatic alkane
contribute to the overall hydrophobic character of the drug. Based on this evaluation, it is no surprise
that the drug undergoes rapid dissolution and solvation in the aqueous contents of the GI tract.
Although it appears that there is only a moderate amount of hydrophobic character, this appears to
be sufficient to allow for absorption across the lipid bilayer membrane.

5. A number of fluvoxamine metabolites have been identified, all of which demonstrate little or no
5. A number of Evaluate each of the which metabolic transformation has occurred.
pharmacological activity. Evaluate each of the metabolic products drawn below and identify which

metabolic transformation has occurred.

A B

C D

F
E