What is the pharmacokinetics (PK) and pharmacodynamics (PD) of cefixime?

Pharmacokinetics and Pharmacodynamics of Cefixime

Pharmacokinetics

Cefixime demonstrates moderate oral bioavailability (40-50%) with a prolonged elimination half-life of 3-4 hours, enabling once or twice-daily dosing regimens. 1

Absorption

• Oral bioavailability: 40-50% regardless of food intake, though food delays time to peak concentration by approximately 0.8 hours 1
• Peak serum concentrations (Cmax):
  • 200 mg tablet: ~2 mcg/mL (range 1-4 mcg/mL) 1
  • 400 mg tablet: ~3.7 mcg/mL (range 1.3-7.7 mcg/mL) 1
  • Oral suspension produces 25-50% higher peak concentrations than tablets 1
  • 400 mg capsule is bioequivalent to tablet under fasting conditions, but food reduces absorption by 15% (AUC) and 25% (Cmax) 1
• Time to peak (Tmax): 2-6 hours for tablets, 2-5 hours for 200 mg suspension, 3-8 hours for capsules 1
• Absorption mechanism: Primarily via carrier-mediated intestinal transport due to the vinyl group at the 3-position of the cephem nucleus 2

Distribution

• Protein binding: Approximately 65%, concentration-independent 1
• CSF penetration: Inadequate data available 1
• Tissue distribution: Minimal accumulation in serum or urine after 14 days of dosing 1

Metabolism and Elimination

• Metabolism: No evidence of in vivo metabolism; drug is excreted unchanged 1
• Renal excretion: Approximately 50% of absorbed dose excreted unchanged in urine within 24 hours 1
• Biliary excretion: >10% of administered dose in animal studies 1
• Elimination half-life: 3-4 hours in healthy adults (range up to 9 hours in some individuals) 1, 3

Special Populations

• Elderly patients: AUC approximately 40% higher than younger adults; half-life increases to 4.2 hours (vs 3.5 hours in young adults) 1
• Renal impairment:
  • Moderate impairment (CrCl 20-40 mL/min): Half-life prolonged to 6.4 hours 1
  • Severe impairment (CrCl 5-20 mL/min): Half-life increases to 11.5 hours 1
  • Not significantly cleared by hemodialysis or peritoneal dialysis 1
• Pediatric patients: The 3-hour elimination half-life permits once or twice-daily dosing at 8 mg/kg 3, 4

Pharmacodynamics

Cefixime exhibits time-dependent bactericidal activity through inhibition of bacterial cell wall synthesis, with particular efficacy against Enterobacteriaceae and respiratory pathogens. 1

Mechanism of Action

• Target: Inhibition of bacterial cell wall synthesis via binding to penicillin-binding proteins (PBPs) 1
• Beta-lactamase stability: Resistant to hydrolysis by many beta-lactamases due to the aminothiazole ring and R-oxyimino group on the 7-position side-chain 1, 2
• Bactericidal kinetics: Time-dependent killing; efficacy correlates with time above MIC rather than peak concentration 3

Antimicrobial Spectrum

• Highly active against:

  • Streptococcus pneumoniae and Streptococcus pyogenes 1, 3
  • Haemophilus influenzae and Moraxella catarrhalis 1, 3
  • Enterobacteriaceae: E. coli, Proteus mirabilis, Klebsiella species 1, 3
  • Neisseria gonorrhoeae (though resistance is increasing) 1

• Limited or no activity against:

  • Staphylococcus aureus (including MRSA) 1, 3
  • Pseudomonas aeruginosa 1, 3
  • Enterococcus species 1
  • Most Enterobacter species 1
  • Bacteroides fragilis and most Clostridium species 1

Clinical PK/PD Considerations

• Dosing frequency: The 3-4 hour half-life and sustained bactericidal activity permit once or twice-daily dosing for most infections 3, 2
• Tissue penetration: Achieves therapeutic concentrations in respiratory tract, urinary tract, and middle ear fluid 3, 4
• Gonorrhea treatment limitations: Provides lower and less sustained bactericidal levels than ceftriaxone 125 mg IM, with only 97.1-97.4% cure rates for urogenital/anorectal gonorrhea versus 99.1% for ceftriaxone 5
• Pharyngeal infections: Limited efficacy against pharyngeal gonorrhea compared to other sites 5

Resistance Mechanisms

• Primary mechanism: Alterations in penicillin-binding proteins (PBPs), particularly in H. influenzae and N. gonorrhoeae 1
• ESBL producers: Limited activity against Enterobacteriaceae producing extended-spectrum beta-lactamases 1
• Rising MICs: Documented increases in minimum inhibitory concentrations, particularly in Western United States and among men who have sex with men for gonococcal infections 5