Some Observations on the Kinetics of the C∙4 Epimerization of Tetracycline

Remmers, Edward G.; Sieger, George M.; Doerschuk, Albert P.

doi:10.1002/jps.2600520809

Cited by 54 publications

(15 citation statements)

References 3 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The epimer of tigecycline was shown to be a degradant rather than a metabolite, inasmuch as it was formed when tigecycline was incubated in control human serum and urine at 37°C (data not shown). Epimerization at the C-4 position has also been reported for structurally similar antibiotics (Remmers et al, 1963;Nelis and De Leenheer, 1982).…”

Section: Discussionmentioning

confidence: 56%

Metabolism, Excretion, and Pharmacokinetics of [¹⁴C]Tigecycline, a First-In-Class Glycylcycline Antibiotic, after Intravenous Infusion to Healthy Male Subjects

Hoffmann

DeMaio²,

Jordan³

et al. 2007

Drug Metab Dispos

View full text Add to dashboard Cite

ABSTRACT:Tigecycline, a novel, first-in-class glycylcycline antibiotic, has been approved for the treatment of complicated intra-abdominal infections and complicated skin and skin structure infections. The pharmacokinetics, metabolism, and excretion of [ 14 C]tigecycline were examined in healthy male volunteers. Tigecycline has been shown to bind to bone; thus, to minimize the amount of radioactivity binding to bone and to maximize the recovery of radioactivity, tigecycline was administered intravenously (30-min infusion) as a single 100-mg dose, followed by six 50-mg doses, every 12 h, with the last dose being [ 14 C]tigecycline (50 Ci). After the final dose, the pharmacokinetics of tigecycline in serum showed a long halflife (55.8 h) and a large volume of distribution (21.0 l/kg), whereas radioactivity in serum had a shorter half-life (6.9 h) and a smaller volume of distribution (3.3 l/kg). The major route of elimination was feces, containing 59% of the radioactive dose, whereas urine contained 32%. Unchanged tigecycline was the predominant drugrelated compound in serum, urine, and feces. The major metabolic pathways identified were glucuronidation of tigecycline and amide hydrolysis followed by N-acetylation to form N-acetyl-9-aminominocycline. The glucuronide metabolites accounted for 5 to 20% of serum radioactivity, and approximately 9% of the dose was excreted as glucuronide conjugates within 48 h. Concentrations of N-acetyl-9-aminominocycline were approximately 6.5% and 11% of the tigecycline concentrations in serum and urine, respectively. Excretion of unchanged tigecycline into feces was the primary route of elimination, and the secondary elimination pathways were renal excretion of unchanged drug and metabolism to glucuronide conjugates and N-acetyl-9-aminominocycline.

show abstract

Section: Discussionmentioning

confidence: 56%

Metabolism, Excretion, and Pharmacokinetics of [¹⁴C]Tigecycline, a First-In-Class Glycylcycline Antibiotic, after Intravenous Infusion to Healthy Male Subjects

Hoffmann

DeMaio²,

Jordan³

et al. 2007

Drug Metab Dispos

View full text Add to dashboard Cite

show abstract

“…The degree of epimerization is increased by several buffers such as phosphates, citrates, or acetates. The kinetics of C4 epimerization in tetracyclines have also been investigated (REMMERS et al 1963).…”

Section: Chemistrymentioning

confidence: 99%

Chemical Modification of the Tetracyclines

Rogalski¹

1985

The Tetracyclines

View full text Add to dashboard Cite

“…The most commonly reported transformation reactions are epimerization, a steric rearrangement in the configuration of the dimethylamino function at C 4 to form epi-tetracycline, and dehydration at C 5a,6 to form anhydrotetracycline (6). The activity of the epimer was found to be less than 5% of the normal analogue while the anhydro product has the potential to cause kidney damage (7). However, dehydration reaction does not occur in MH due to the lack of jOH group at C 6 (6).…”

Section: Introductionmentioning

confidence: 98%

Formulation of Hydrophilic Non-Aqueous Gel: Drug Stability in Different Solvents and Rheological Behavior of Gel Matrices

2007

View full text Add to dashboard Cite

show abstract

Some Observations on the Kinetics of the C∙4 Epimerization of Tetracycline

Cited by 54 publications

References 3 publications

Metabolism, Excretion, and Pharmacokinetics of [¹⁴C]Tigecycline, a First-In-Class Glycylcycline Antibiotic, after Intravenous Infusion to Healthy Male Subjects

Metabolism, Excretion, and Pharmacokinetics of [¹⁴C]Tigecycline, a First-In-Class Glycylcycline Antibiotic, after Intravenous Infusion to Healthy Male Subjects

Chemical Modification of the Tetracyclines

Formulation of Hydrophilic Non-Aqueous Gel: Drug Stability in Different Solvents and Rheological Behavior of Gel Matrices

Contact Info

Product

Resources

About

Some Observations on the Kinetics of the C∙4 Epimerization of Tetracycline

Cited by 54 publications

References 3 publications

Metabolism, Excretion, and Pharmacokinetics of [14C]Tigecycline, a First-In-Class Glycylcycline Antibiotic, after Intravenous Infusion to Healthy Male Subjects

Metabolism, Excretion, and Pharmacokinetics of [14C]Tigecycline, a First-In-Class Glycylcycline Antibiotic, after Intravenous Infusion to Healthy Male Subjects

Chemical Modification of the Tetracyclines

Formulation of Hydrophilic Non-Aqueous Gel: Drug Stability in Different Solvents and Rheological Behavior of Gel Matrices

Contact Info

Product

Resources

About

Metabolism, Excretion, and Pharmacokinetics of [¹⁴C]Tigecycline, a First-In-Class Glycylcycline Antibiotic, after Intravenous Infusion to Healthy Male Subjects

Metabolism, Excretion, and Pharmacokinetics of [¹⁴C]Tigecycline, a First-In-Class Glycylcycline Antibiotic, after Intravenous Infusion to Healthy Male Subjects