CLINICAL PHARMACOLOGY
Human Pharmacology
Cephalexin is acid stable and may be given without regard to meals. It is rapidly absorbed after oral administration. Following doses of 250 mg, 500 mg, and 1 g, of conventional cephalexin, average peak serum levels of approximately 9, 18, and 32 mcg/mL respectively were obtained at 1 hour. Measurable levels were present 6 hours after administration.
Following a dose of Ranbaxy’s Panixine DisperDose tablets, equivalent to 500 mg of cephalexin, the average peak serum level of 15.25 mcg/mL was obtained at 1 hour. Following a dose of conventional cephalexin suspension equivalent to 500 mg of cephalexin, the average peak serum level of 14.67 mcg/mL was obtained at 1 hour. Measurable levels were present 6 hours after administration of Ranbaxy’s Panixine DisperDose.
Cephalexin is excreted in the urine by glomerular filtration and tubular secretion. Studies showed that over 90% of the drug was excreted unchanged in the urine within 8 hours. During this period, peak urine concentrations following the 250 mg, 500 mg, and 1 g doses were approximately 1,000, 2,200, and 5,000 mcg/mL respectively.
Microbiology
In vitro tests demonstrate that the cephalosporins are bactericidal because of their inhibition of cell-wall synthesis. Cephalexin has been shown to be active against most strains of the following microorganisms both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section.
Aerobes, Gram-positive:
Staphylococcus aureus (including penicillinase-producing strains)
Staphylococcus epidermidis (penicillin-susceptible strains)
Streptococcus pneumoniae
Streptococcus pyogenes
Aerobes, Gram-negative:
Escherichia coli
Haemophilus influenzae
Klebsiella pneumoniae
Moraxella (Branhamella) catarrhalis
Proteus mirabilis
Note — Methicillin-resistant staphylococci and most strains of enterococci (Enterococcus faecalis [formerly Streptococcus faecalis ]) are resistant to cephalosporins, including cephalexin. It is not active against most strains of Enterobacter spp, Morganella morganii, and Proteus vulgaris. It has no activity against Pseudomonas spp or Acinetobacter calcoaceticus.
Susceptibility Tests
Diffusion techniques:
Quantitative methods that require measurement of zone diameters provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. One such standardized procedure1 that has been recommended for use with disks to test the susceptibility of microorganisms to cephalexin uses the 30 mcg cephalothin disk. Interpretation involves correlation of the diameter obtained in the disk test with the minimal inhibitory concentration (MIC) for cephalexin.
Reports from the laboratory providing results of the standard single-disk susceptibility test with a 30 mcg cephalothin disk should be interpreted according to the following criteria:
| Zone Diameter (mm) | Interpretation |
| ≥ 18 | (S) Susceptible |
| 15 to 17 | (I) Intermediate |
| ≤ 14 | (R) Resistant |
A report of “Susceptible” indicates that the pathogen is likely to be inhibited by usually achievable concentrations of the antimicrobial compound in blood. A report of “Intermediate” indicates that the result should be considered equivocal, and, if microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where high dosage of drug can be used. This category also provides a buffer zone that prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of “Resistant” indicates that usually achievable concentrations of the antimicrobial compound in the blood are unlikely to be inhibitory and that other therapy should be selected.
Measurement of MIC or MBC and achieved antimicrobial compound concentrations may be appropriate to guide therapy in some infections. (See CLINICAL PHARMACOLOGY section for information on drug concentrations achieved in infected body sites and other pharmacokinetic properties of this antimicrobial drug product.)
Standardized susceptibility test procedures require the use of laboratory control microorganisms. The 30 mcg cephalothin disk should provide the following zone diameters in these laboratory test quality control strains:
| Microorganism | Zone Diameter (mm) |
| E. coli ATCC 25922 | 15 to 21 |
| S. aureus ATCC 25923 | 29 to 37 |
Dilution techniques
Quantitative methods that are used to determine MICs provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. One such standardized procedure uses a standardized dilution method2 (broth, agar, microdilution) or equivalent with cephalothin powder. The MIC values obtained should be interpreted according to the following criteria:
| MIC (mcg/mL) | Interpretation |
| ≤ 8 | (S) Susceptible |
| 16 | (I) Intermediate |
| ≥ 32 | (R) Resistant |
Interpretation should be as stated above for results using diffusion techniques.
As with standard diffusion techniques, dilution methods require the use of laboratory control microorganisms. Standard cephalothin powder should provide the following MIC values:
| Microorganism | MIC (mcg/mL) |
| E. coli ATCC 25922 | 4 to 16 |
| E. faecalis ATCC 29212 | 8 to 32 |
| S. aureus ATCC 29213 | 0.12 to 0.5 |
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