Cloxacillin : Serum Level

Recommended Plasma Concentration

According to the European Committee on Antimicrobial Susceptibility Testing (EUCAST), the MIC threshold to determine the strain sensitivity is 2 mg/L for cloxacillin.
Until now, the optimal plasma concentration target in order to achieve the best cure rate remains undefined, but as oxa- and cloxacillin are time-dependent antibiotics, a time of 100% above the minimum inhibitory concentration (MIC) was considered to be optimal for efficacy.
Considering that oxa- and cloxacillin are highly bound to albumin and that their unbound fraction—the available fraction for antibiotic efficacy—in healthy patients is known to be 10%,
Previous study indicated that a dosing regimen of 1 g dicloxacillin every 6 hours should be effective for S. aureus infections with a mean MIC value of 0.125 µg·mL⁻¹ (achieving 67%T > MIC) (higher bioavailability compared to cloxacillin, 48.8% versus 36.9%)

Population: severe infections treated in ICU

Defined a target range of total antibiotic concentration of 20–50 mg/L to reach the 100% T > MIC
At a Median Daily Dosing of 105.5mg/kg [75; 150] produced a median plasma concentration of 134.3mg/L [65.3; 201].
Using a percentage of 10% to estimate the unbound fraction of oxa- or cloxacillin, all patients would have had a trough unbound fraction concentration superior or equal to the maximum MIC for oxa- or cloxacillin sensitivity, i.e. 2 mg/L

Oral Cloxacillin

At a dose of 2g, average calculated dose based on serum concentration was 649mg (32.9%).
Oral dose of 500mg cloxacillin produced a peak serum level of 8mcg/ml in adults
After an oral dose of 500 mg, a peak plasma concentration of 7 to 14 μg per mL is attained in fasting subjects in 1 to 2 hours.
After an oral dose of 500mg cloxacillin, a peak serum level of about 8 micrograms/mL is reached in about 1 hour.

PHARMACOKINETICS OF FLUCLOXACILLIN AND CLOXACILLIN IN HEALTHY SUBJECTS AND PATIENTS ON CHRONIC INTERMITTENT HAEMODIALYSIS. Br. J. clin. Pharmac. (1975), 2, 111-121
Infectious Diseases of the Female Genital Tract. By Richard L. Sweet, Ronald S. Gibbs
Cloxigen Product Information Leaflet

Intramuscular

serum level after i.m. cloxacillin is approximately twice that obtained when the same dose is given orally to fasting adults

Concentration in Synovial tissue

After a 30 min i.v. infusion of 1 g cloxacillin, the concentrations of this antibiotic were measured in plasma and synovial tissue samples from 11 patients undergoing total hip replacement.
The concentration of free drug in synovial tissue was estimated to be 77% of the total tissue concentration.
The maximum tissue drug concentration after an i.v. bolus dose is predicted to occur at about 37 min.
it can be predicted that after an i.v. bolus injection of 1 g cloxacillin the maximum synovial tissue concentration will be reached at 37 min after administration. At this time the estimated free drug concentrations in plasma and tissue should be 0.9 mg/l.