The Development History and Existing Forms of Ceftiofur

Ceftiofur is a third-generation β-lactam cephalosporin for livestock and poultry. It has strong antibacterial activity, excellent pharmacokinetic properties, low toxicity and side effects, and low residue. It has strong antibacterial effects on both Gram-positive and Gram-negative bacteria. Ceftiofur acts on transcriptopeptidases, blocks the synthesis of mucopeptides, and causes the bacterial cell wall to fall off, thereby achieving a bactericidal effect. Ceftiofur has a stable β-lactam ring, which is not easily destroyed by drug-resistant bacteria and can act on β-lactamase-producing Gram-positive and Gram-negative bacteria.

Development History

In 1984, Ceftiofur was first synthesized by Bernard et al., and then Pharmacia Upjohn produced Ceftiofur sodium salt freeze-dried powder and hydrochloride suspension, which were widely used in the treatment of animal diseases.

In 1988, the US FDA used it for the first time to treat bacterial respiratory diseases in cattle. Subsequently, ceftiofur hydrochloride, ceftiofur sodium and ceftiofur crystalline free acid were approved for the treatment of respiratory diseases in pigs, cattle, horses and sheep.

Synthesis

The synthesis of ceftiofur mainly uses 7-aminocephalosporanic acid (7-ACA) as raw material, and ceftiofur acid is obtained by condensation reaction at the 3rd position and amidation reaction at the 7th position, and then reacts with concentrated hydrochloric acid to obtain ceftiofur hydrochloride, and finally ceftiofur hydrochloride is converted into ceftiofur sodium salt.

Form of existence

Ceftiofur exists in crystalline form, which can be sodium salt or hydrochloride. Amorphous ceftiofur is difficult to exist independently and cannot be made into drugs; in addition, ceftiofur acid crystals and its hydrochloride are insoluble in water, and only ceftiofur sodium is soluble in water.

Ceftiofur sodium is the sodium salt form of ceftiofur, with an active ingredient content of not less than 85%, easily soluble in water, a half-life of about 14 hours, high blood drug concentration, short peak time, easy to take effect quickly, and easy to inject.

Ceftiofur hydrochloride is the hydrochloride form of ceftiofur, with an active ingredient content of not less than 85%, insoluble in water, a suspension, a half-life of about 20 hours, and a long-lasting effect.

Ceftiofur free acid is a free acid form, with an active ingredient content of not less than 93%, insoluble in water, a half-life of about 40 hours, a blood drug concentration lower than ceftiofur sodium, a long-acting sustained-release effect, and is suitable for medical care.