Novobiocin salts

Incompatibilities Do not mix IV minocycline before or during administration with any solutions containing the following Adrenocorticotropic hormone (ACTH), aminophylline, amobarbital sodium, amphotericin B, bicarbonate infusion mixtures, calcium gluconate or chloride, carbenicillin, cephalothin sodium, cefazolin sodium, chloramphenicol succinate, colistin sulfate, heparin sodium, hydrocortisone sodium succinate, iodine sodium, methicillin sodium, novobiocin, penicillin, pentobarbital, phenytoin sodium, polymyxin, prochlorperazine, sodium ascorbate, sulfadiazine, sulfisoxazole, thiopental sodium, vitamin K (sodium bisulfate or sodium salt), whole blood. 

The sodium or potassium salts of weak acids have higher absorption rate than those of acids themselves. For example, the biological activity of sodium salt of novobiocin (weak acid) is twice as compared to its calcium salt, and about 50 times larger in comparison to its free acid. 

Novobiocin [303-81-1] M 612.6, two forms m 152-156" and m 174-178", X ax.330nm (acid EtOH), 305nm (alk EtOH), [cx]p (c 1, EtOH). Crystd from EtOH and stored in the dark. The sodium salt can be crystd from MeOH, then dried at 60"/0.5mm. [Sensi, Gallo and Chiesa AC 29 1611 1957. ... 

Examples of the use of soluble salts to increase drag absorption include novobiocin, in which the bioavailability of the sodium salt of the drag is twice that of the calcium salt and 50 times that of the free acid. 

Efflux pumps belonging to the resistance-nodulation-division (RND) family are especially effective in generating resistance and often have a wide substrate specificity. An extreme case is the AcrB pump of E. coli, which pumps out the antibiotics tetracychne, chloramphenicol, 6-lactams, novobiocin, fusidic acid, nalidixic acid and fluoroquinolones, as well as detergents, bile salts, various cationic dyes, disinfectants and even solvents. 

The sodium salt of novobiocin is unstable in aqueous solution while the crystalline free acid is inadequately absorbed from the gastrointestinal tractJ ° Consequently, the amorphous Ca salt of novobiocin is employed in liquid formulations because of its stability and bioavailability attributes. 

The large hydrophobic compound XIX, even as its hydrochloride salt, is poorly soluble and this is presumably the reason for its poor oral bioavailability. Similar conclusions were drawn several years ago for novobiocin. The acid salt administered at 12.5 mg kg to dogs was not absorbed, but the monosodium salt, which is about 300 times as soluble in water, produced plasma levels of 22 /rg cm after 3 hours. Unfortunately, the sodium salt is unstable in solution. An amorphous form of the acid produced even higher levels of dmg than the sodium salt, illustrating the fact that choice of salt and crystalline form of a dmg substance may be of critical importance. 

Novobiocin is a pale yellow, somewhat photosensitive compound that crystallizes in two chemically identical forms with different melting points (polymorphs). It is soluble in methanol, ethanol, and acetone but is quite insoluble in less polar solvents. Its solubility in water is affected by pH. It is readily. soluble in basic solutions, in which it deteriorates, and is precipitated from acidic solutions. It behaves as a diacid, forming two. series of salts. 

The enolic hydroxyl group on the coumarin moiety behaves as a rather strong acid (pKa 4.3) and is the group by which the commercially available sodium and calcium salts arc formed. The phenolic -OH group on the benzamido moiety also behaves as an acid but is weaker than the former, with a pKa of 9.1. Disodium salts of novobiocin have been prepared. The. sodium salt is stable in dry air but loses activity in the presence of moisture. The calcium salt is quite water insoluble and is used to make aqueous oral suspensions. Because of its acidic characteristics, novobiocin combines to form salt complexes with basic antibiotics. Some of the.se saits have been investigated for their combined antibiotic effect, but none has been placed on the market, as they offer no advantage. 

Table 8.2 Differences in Novobiocin plasma levels as a function of salt form, crystalline form, and amorphous form...

Novobiocin is marketed under the following trade names Albamydn, Biotexin, Cathocin, Cathomycin, Inamycin, Spheromycin, Vulcamycin and Vulkamycin. The antibiotic is soluble in aqueous solution above pH 7-5 [7] and in polar organic solvents. It is stable in the dark, but is slightly light-sensitive (7]. In practice, it is used either as the mono- or di-sodium salt or as the calcium salt. 

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