Dear Mansor Zarrabi,

as clinical pharmacist i will try to answer on your answer, which is very interesting and has many of clinical implications.

1) nitrate, sulfate, fluoride, carbonate are anions and therefore drug drug interactions with anions are almost impossible, however interactions with anions are possible.

2) you mean hardness of water? There are CaCO3 and MgCO3 in the water and therefore drug drug interactions with cations (CO3) and anions (Ca and Mg) are possible. More hardness is water more interactions with anions are possible.

Usually the drug drug interactions with ionic bond are more possible in drugs where there is high difference between + and -. For example sulfate is more negative than carbonate.

If we look now on your compounds ...:

1) tetracycline: especially OH on benzene ring is relative good acid and therefore interactions with cations are possible (more hard water less absorption takes place). Next to the ionic bond there is possible to make complex with calcium and magnesium and tetracycline. This has also clinical consequences and because of that reason we suggest the patients not to take these drugs with hard water, food with calcium etc ...

Complexes with anions are less possible, because we do not have positive centre (e.g.secondary amine is almost acidic in this case).

2) Metronidazole: less interactions are possible, maybe only with cations and NO2 group. With anions we do not have DDIs.

3) Carbamazepine: Almost no problem with this type of interactions (amide group is acidic) and DDIs with cations would be more possible.

4) sulfamethoxazole: Especially interactions with cations are possible and with strong anions. If one acid is more acidic (sulfate) than other (Ph-NH2) then other acid acts as base (PH-NH2) and interactions with strong anions are also possible. For these conclusions you need pKa values for all compounds.

Regards,

Mathew

Dear Dr. Matej Stuhec

Hello and many thanks for your great effort. Do you can please send me your references in this regards?

Dear Mansor,

i put the knowledge of my medicinal chemistry and clinical pharmacy inside.

However, check the following book entitled: https://books.google.si/books/about/Foye_s_Principles_of_Medicinal_Chemistry.html?id=R0W1ErpsQpkC&hl=en

Regards,

Matej

Dear Prof. Matej

Thank you so much for sharing good news with me. do you can email this book for me?

Dear Mansor,

I am very sorry but i have only book (paper) version.

Please check out on Amazon if you want to order etc...

Regards,

Matej

Dear Prof. Matej

Thank you for your kind reply