Total hip joint arthroplasty with gentamicin-impregnated cement. A clinical study of gentamicin excretion kinetics

The excretion pharmacokinetics of gentamicin (GM) following total hip joint arthroplasty with GM-impregnated bone cement were studied in ten patients. The patients received 0.5-1.1 g of GM. Twenty-four-hour portions of urine were collected for up to 60 days after operation. GM concentrations in urine were initially 8-25 mg/l, and during the first four days the excretion ranged from 0.7 to 25 mg/day. On the 30th day drug levels in the urine were 0.5-1.0 mg/l, and the excretion was 0.5-1.0 mg/day. The GM excretion-time curve consisted of an initial rapid phase that terminated four to six days after operation, with a half-life of 0.65 days, and a slow phase with a half-life of 7.5-73.0 days (mean, 16 days). From the area under the excretion-time curve and from extrapolation of the registered terminal phase, it was calculated that 5%-18% (mean, 13%) of the GM administered was accounted for. Thus, a major portion of the drug was unaccounted for. Data obtained two years after operation suggested that the half-life of the terminal phase is much longer (greater than 240 days) than that calculated from data obtained during the first two months after operation. It was calculated that the surface area of the cement would be in excess of 150 cm2 and that the volume of an interface tissue layer 1 mm thick would be approximately 15 cm3. Thus, at three weeks, when the daily excretion was approximately 1 mg/24 hours, 67 micrograms/cm3/day of GM would be available for antimicrobial action at a tissue--cement interface 1 mm thick.