Pharmacokinetics of intraperitoneal teicoplanin in patients with chronic renal failure on continuous ambulatory peritoneal dialysis.

Abstract

The pharmacokinetic profile of teicoplanin, a new glycopeptide antibiotic active against Gram‐positive aerobic and anaerobic bacteria, is described in five patients with end‐stage renal disease on continuous ambulatory peritoneal dialysis (CAPD). A single 3 mg kg‐1 dose was given intraperitoneally in the dialysate during a 6 h dwell time. The drug appeared in the plasma within 15 min at 1.00‐0.28 mg l‐1 (mean +/‐ s.d. = 0.70 +/‐ 0.45) in all five subjects, and peak serum concentrations ranged from 5.53 to 2.80 mg l‐1 (4.84 +/‐ 1.43) at 6 h. Approximately 70% (71 +/‐ 12) of teicoplanin was absorbed from the peritoneal dialysis fluid during a single 6 h dwell time. The rate constant for peritoneal transfer (lambda d) averaged 0.318 h‐1 and the half‐life (t1/2 lambda d) was 2.18 h. Further values were serum elimination half‐life 114‐173 h; total body clearance 263‐532 ml h‐1; steady‐state volume of distribution 68‐93 l. This drug profile closely agrees with data reported after intravenous injection in patients on CAPD and suggests that teicoplanin has bidirectional exchange characteristics through the peritoneal membrane, although transfer from the systemic circulation to peritoneal fluid is consistently low. Instillation of teicoplanin in CAPD fluid may be a useful route of administration for treatment of peritonitis and exit site infections in CAPD patients.

Intermittent versus Continuous Intraperitoneal Glycopeptide/Ceftazidime Treatment in Children with Peritoneal Dialysis-Associated Peritonitis

“…Because of the markedly prolonged half-life of vancomycin in chronic renal insufficiency, it was proposed that vancomycin be administered intermittently by two bolus doses 7 d apart, using the patient's body as a reservoir for the drug. Teicopla-nin, another glycopeptide antibiotic with an even longer halflife in uremic patients due to higher protein binding (7,8) and a reportedly milder adverse effect profile (9), might be an attractive alternative to vancomycin for intermittent administration, but the experience with its use in CPD-related peritonitis is limited (10,11). As the elimination of ceftazidime is also diminished in uremia, intermittent dosing should also be possible (12,13).…”