Cefadroxil
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Cephalosporins
The basic nucleus of the cephalosporins is 7 amino cephalosporanic
acid. This is composed of a ß-lactam ring and a dihydrothiazine
ring
|
Cephalosporins
First
generation |
Second
generation
|
Third
generation
|
Cephalothin
|
Cefamandole
|
Cefotaxime
|
Cefazolin
|
Cefoxitin
|
Moxalactam
|
Cephapirin
|
Cefuroxime
|
Cefoperazone
|
Cephradine
|
Cefaclor
|
Ceftizoxime
|
Cephalexin
|
|
Ceftriaxone
|
Cefadroxil
|
|
Ceftazidime
|
|
|
Cefsulodin
|
|
|
Cefmenoxime
|
|
|
Cefixime
|
|
Cephalosporins
- Spectrum
Relative
antibacterial coverage of cephalosporins by generation
Generation
|
gm
+ve |
gm
-ve |
First
generation |
+++ |
+
|
Second
generation |
++ |
++ |
Third
generation |
+ |
+++
|
|
The
OH group makes the difference!
The addition
of the para-hydroxyl group (OH) on the aromatic ring of cephalexin
alters the pharmacokinetic properties of cephalexin and creates the
new drug, cefadroxil
|
Cefadroxil
Mechanism
of Action
- Bactericidal
- Act by inhibition of bacterial cell wall synthesis
|
Spectrum
Similar
to cephalexin
Important
organisms
Staph. aureus
Strep. pyogenes
Strep. pneumoniae
E. coli
Proteus mirabilis
Klebsiella pneumoniae
H. influenzae
|
Pharmacokinetics
Cefadroxil
is superior to cephalexin because of better pharmacokinetics.
These include
- Higher serum concentrations
- Better lipid solubility results in better penetration into body
tissues and fluids
- Slower excretion, hence longer duration of action- Higher AUC (area
under plasma concentration - time curve)
|
Absorption
Cefadroxil
is well absorbed on oral administration; food does not interfere with
the absorption
Distribution
-
Better lipid solubility than cephalexin facilitates superior penetration
into body tissues and fluids. - Good concentrations in tonsils, lungs,
bone, muscle, synovial capsule, prostate, gynaecological tissues and
body fluids including sputum, pleural fluid, skin blisters and aqueous
humour
|
Metabolism
& Excretion
- Cefadroxil
is not metabolised in the body
- Excreted unchanged in urine
- Plasma half-life 1-1.5 hours; twice that of cephalexin
|
Indications
1. Lower Respiratory
Tract Infections
2. Pharyngitis
3. Otitis media
4. Skin & Soft Tissue Infection
5. Bone & Joint Infection
6. Urinary Tract Infection
7. Prostatitis
8. Biliary Tract Infection
|
Dosage
Usual dosage
for adults
500 mg twice daily
Children
30-50 mg/kg/day in divided doses
Renal Failure
- Creatinine clearance 10-25 ml/min
administer
dose every 24 hours
- Creatinine
clearance 0-10 ml/min
administer
dose every 36 hours
|
Adverse Effects
- Uncommon
- Nausea, vomiting, diarrhoea, allergic rashes
may occur
- Safe in pregnancy
Contraindications
- Hypersensitivity
|
Salient Features
- Broad antibacterial
spectrum
- Resistant to inactivation by b-lactamases
- Good GI absorption
- High and prolonged concentration in plasma, urine, body tissues
and fluids
- Widely distributed; better tissue penetration than cephalexin
- Long plasma half life
- Prolonged duration of action
- Convenient twice daily dosing
- Well tolerated
|
Advantages over Cephalexin
- Similar antibacterial
spectrum
- Superior and more prolonged tissue concentrations
- Convenient b.d. dosing compared to q.I.d. dosing with cephalexin
- Better compliance with simpler dosing may result in greater efficacy
|
Advantages
over penicillins
(Ampicillin,
Amoxycillin)
- Effective
against organisms resistant to penicillins
- May be tried in patients who are hypersensitive to penicillins
|
Advantages over fluoroquinolones
(Ciprofloxacin, Norfloxacin)
- Fluoroquinolones
are chiefly indicated for gram negative infections; cefadroxil may
be preferred for gram positive infections
- Cefadroxil is safe in children and in pregnancy; fluoroquinolones
are better avoided here
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