PHARMACOKINETICS OF CEFTRIAXONE IN LIVER-TRANSPLANT RECIPIENTS

The disposition of ceftriaxone was studied after a single 2 g intravenous dose in seven patients 3 to 5 days after liver transplantation. Ceftriaxone concentrations in plasma, urine, and bile were measured by HPLC, and plasma protein binding was determined by equilibrium dialysis. Plasma protein binding was nonlinear, and the unbound fraction varied between 0.05 and 0.56. Both capacity and affinity were markedly different from reported values for normal subjects. The pharmacokinetic parameters obtained were: total body clearance (TBC), 11.2 +/- 7.8 mL/hr/kg total and 44.8 +/- 29.1 mL/hr/kg unbound; volume of distribution (V(area)), 224 +/- 76 mL/kg total and 767 +/- 432 mL/kg unbound; steady-state volume of distribution (V(ss)), 212 +/- 68 mL/kg total and 651 +/- 368 mL/kg unbound; terminal disposition half-life (t1/2), 21.6 +/- 14.3 hour total and 16.3 +/- 11.1 hour unbound. TBC for both total and free drug was considerably lower than literature values for normal subjects. V(area) for total drug was greater than normal, whereas the corresponding value for free drug was smaller than normal. The plasma ceftriaxone concentrations at 12 and 24 hours were above the reported minimum inhibitory concentration (MIC). The fraction of the administered dose excreted in urine over 24 hours was 38 +/- 29% and did not differ markedly from that reported for normal subjects. Less than 2% of the administered dose was excreted in 24-hour bile; however, biliary concentrations were always above MIC. Ceftriaxone can be administered once or twice daily at a dose of 2 g/day for prophylaxis in liver transplant recipients.