Abstract
We developed an initial dosage regimen for vancomycin hydrochloride (VCM) therapy based on over-dosing range (IOR) incidence determined from the relationship between trough levels and estimated creatinine clearance (CLcr) in 276 patients from Chubu, Chugoku and Kumamoto Rosai hospitals using assumed daily doses of 500, 1000 and 2000 mg. We divided the patients into two groups, a once-a-day group (77) and a twice-a-day group (199), according to the method of administration.
The predicted concentrations of VCM at trough levels (Cp-t) at 500, 1000, and 2000 mg/day were calculated as level/dose ratios. The IOR was determined from the incidence of VCM levels greater than 15μg/mL in patients with different CLcr rates.
An assumed dosage of 500 mg/day produced an adequate VCM level range in patients with CLcr≥30 mL/min but the VCM level range was not adequate in patients with CLcr<50 mL/min.
In the case of the 1000 and 2000 mg/day dosages, the IOR was calculated to be about 5.6% in patients with CLcr≥50 mL/min and up to 15% for those with CLcr≥80 mL/min. The influence of age on IOR based on Cp-t was not significant.
Using our results, we determined a VCM dosage regimen based on renal function : 500 mg/day for a CLcr of 30-40 mL/min ; 1000 mg/day for a CLcr greater than 50 mL/min and 2000 mg/day for a CLcr greater than 80 mL/min. We concluded that a dosage regimen based on IOR is appropriate for determining the initial dosage of VCM.
