Cefuroxime

Pharmacological Actions
Cefuroxime exerts its primary pharmacological action as a β-lactam antibiotic, specifically targeting bacterial cell wall synthesis. It inhibits the final transpeptidation step of peptidoglycan synthesis by binding to penicillin-binding proteins (PBPs) within the bacterial cell wall. This interference weakens the cell wall, leading to bacterial lysis and death, classifying it as bactericidal. It is effective against a broad spectrum of bacteria, including:

Gram-positive: Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes
Gram-negative: Escherichia coli, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Moraxella catarrhalis, Neisseria gonorrhoeae
Other: Borrelia burgdorferi (relevant for Lyme disease)

This broad-spectrum activity makes Cefuroxime suitable for treating various infections, including upper and lower respiratory tract infections, urinary tract infections, skin and soft tissue infections, and early Lyme disease.
Pharmacokinetics: Half-Life and Bioavailability
Half-Life:
The half-life of Cefuroxime, which indicates the time taken for the plasma concentration to reduce by half, is approximately 1-2 hours in adults for both oral and parenteral administration. This duration can extend in patients with impaired renal function, as the drug is primarily excreted unchanged by the kidneys. For children, the half-life ranges from 1.4 to 1.9 hours, influenced by age and renal function.
Bioavailability:
Bioavailability, or the fraction of the drug absorbed into systemic circulation, varies by route:

Oral (Cefuroxime axetil): When taken on an empty stomach, bioavailability is 37%, but it increases to 52% when administered with food. This enhancement is due to improved absorption in the presence of food, which may reduce gastrointestinal degradation.
Parenteral (IV/IM): For intravenous (IV) and intramuscular (IM) administration, bioavailability is effectively 100%, as the drug is directly introduced into the bloodstream. Peak serum concentrations are achieved rapidly, within 2-3 minutes post-IV and 30-45 minutes post-IM.

Time to peak concentration (Tmax): 2-3 hours for oral in adults, 3-4 hours in children.
Volume of distribution: 0.25-0.3 L/kg, with 33-50% plasma protein binding, allowing penetration into tissues like tonsils, lungs, and bone.

Dosage Regimens and Safety Ranges
Dosage for Cefuroxime varies based on the infection type, route of administration, patient age, and renal function. Below is a detailed breakdown:
Adults:

Pharyngitis/tonsillitis: 250 mg every 12 hours for 10 days.
Sinusitis: 250 mg every 12 hours for 10 days.
Bronchitis: 250-500 mg every 12 hours for 10 days.
Uncomplicated urinary tract infections (UTIs): 125-250 mg every 12 hours for 7-10 days.
Gonorrhea: 1.5 g IM as a single dose at two sites, often with 1 g oral probenecid.
Early Lyme disease: 500 mg every 12 hours for 20 days.

Lower respiratory tract infections, including pneumonia: 750 mg every 8 hours.
Skin and skin structure infections: 750 mg every 8 hours.
Meningitis: Up to 3 g every 8 hours, with a maximum daily dose of 9 g in severe cases.

Oral: Pharyngitis/tonsillitis: 20 mg/kg/day divided every 12 hours, maximum 500 mg/day.
Parenteral: 75-150 mg/kg/day divided every 8 hours, maximum 6 g/day.

For CrCl 10-30 mL/min, oral doses may be given every 24 hours; for CrCl <10 mL/min, every 48 hours.
Parenteral: For CrCl 10-20 mL/min, 750 mg twice daily; for CrCl <10 mL/min, 750 mg once daily.
Hemodialysis patients may require an additional dose post-dialysis.

The safe range aligns with prescribed doses for specific indications, typically 250-500 mg orally every 12 hours for mild to moderate infections in adults.
The minimum effective dose varies by infection and pathogen sensitivity, often starting at 125 mg for UTIs.
The maximum safe dose without high risks is generally the highest recommended dose, such as 500 mg orally every 12 hours or 1.5 g IV/IM every 8 hours, with higher doses (e.g., 3 g every 8 hours for meningitis) used under close monitoring.

LD50: Animal studies indicate an intravenous LD50 of 10.4 g/kg in mice, with higher doses tolerated in other species (e.g., 10 g/kg subcutaneous in mice, 4 g/kg IV in rats). However, human LD50 data are not available, and extrapolation from animal studies should be done cautiously.
Toxicity and Overdose: Overdose can lead to neurological sequelae, including encephalopathy, convulsions, and coma, particularly in patients with renal impairment if doses are not adjusted. Serum levels can be reduced by hemodialysis or peritoneal dialysis. Other toxicities include:

Neurotoxicity, especially in the elderly or those with severe renal impairment or central nervous system disorders.
Potential renal impairment when used concurrently with potent diuretics or aminoglycosides, requiring monitoring.
Overgrowth of non-susceptible microorganisms, such as Candida and Clostridium difficile, potentially leading to pseudomembranous colitis.
Severe cutaneous adverse reactions (SCARs) like Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms (DRESS), which can be life-threatening.

Estimation of When It Becomes Too Dangerous:
The risk increases significantly in patients with renal impairment if doses are not adjusted, leading to drug accumulation and potential neurotoxicity. Concurrent use with nephrotoxic drugs further heightens this risk. For patients with normal renal function, adhering to recommended doses is generally safe, but exceeding these, especially without medical supervision, can lead to serious adverse effects, particularly neurological and renal complications.
Pharmacodynamic Considerations and Time Influence
The user’s request for “values for each time to know how each pharmacological action influences” may refer to pharmacokinetic-pharmacodynamic (PK-PD) relationships, particularly how drug concentrations over time affect efficacy. For cephalosporins like Cefuroxime, the key PK-PD index is the percentage of the dosing interval that the unbound concentration remains above the minimum inhibitory concentration (MIC) of the target pathogen (%T>MIC). Research suggests that for gram-positive bacteria, efficacy is associated with %T>MIC of 40-50%, and for gram-negative bacteria, 60-70%. Specific values depend on the pathogen’s MIC, which varies, but generally:

Peak concentrations are achieved within hours (2-3 hours orally, minutes IV), influencing early bactericidal activity.
With a half-life of 1-2 hours, multiple doses every 8-12 hours maintain therapeutic levels, ensuring sustained activity above MIC.