PHARMACOKINETICS AND BIOAVAILABILITY OF FLUCLOXACILLIN IN ELDERLY HOSPITALIZED-PATIENTS

The pharmacokinetics and oral bioavailability of flucloxacillin were s tudied in five female and two male patients (age 68-87 yr) who had bee n hospitalized for orthopedic surgeries. A single dose of intravenous or oral flucloxacillin sodium (500 mg) was administered in random orde r on different occasions separated by at least 2 days. Blood and urine samples were taken up to 24 hours after drug administration and level s of flucloxacillin and 5-hydroxymethylfluclozacillin (5-HMF), a major metabolite, were measured by high-performance liquid chromatography. Fluclozacillin elimination, but not oral absorption, was reduced in th e elderly, compared with data from young healthy subjects reported els ewhere. Total clearance, renal clearance, and volume of distribution w ere 0.083+/-0.013 L/kg/hr, 0.038+/-0.01 L/kg/hr, and 0.184+/-0.034 L/k g, respectively. Regression of flucloxacillin renal clearance (Cl-r) o n estimated creatinine clearance (CL(cr)) gave the relationship: Cl-r = 0.755 (CL(cr)) + 10.6 (r = 0.91; P = 0.004). Terminal half-lives for flucloxacillin and 5-HMF were 2.21+/-0.51 hr and 3.0+/-0.75 hr, respe ctively, after intravenous administration. Flucloxacillin was absorbed rapidly after oral administration, with a mean absorption time of 0.9 5+/-0.34 hr, and time to reach peak concentration of 1.20+/-0.29 hr. T he absolute bioavailability of flucloxacillin from capsules was 54.4+/ -18.8%.