Teicoplanin pharmacokinetics in patients undergoing continuous ambulatory peritoneal dialysis after intravenous and intraperitoneal dosing

Abstract

The pharmacokinetics of teicoplanin after single 6-mg/kg intravenous and intraperitoneal doses were studied in five noninfected patients undergoing continuous ambulatory peritoneal dialysis. Biological samples were assayed for teicoplanin content (9,23,28). Numerous studies in humans have documented its efficacy in the treatment of septicemia, endocarditis, and skin and skin structure infections caused by these organisms (2,5,11,15,16,29,31,32).Preliminary human pharmacokinetic data suggest that teicoplanin can be administered less frequently than vancomycin owing to its prolonged terminal disposition half-life (t12). In addition, excellent tolerability and bioavailability after intramuscular injection have been reported (4, 12, 20, 21, 24-26, 30, 33). Renal excretion of unchanged teicoplanin is a major route of drug elimination, and preliminary dosage adjustment recommendations for patients with renal impairment have been published (1,6,7,17,27). However, few data exist on the pharmacokinetics of teicoplanin in patients receiving continuous ambulatory peritoneal dialysis (CAPD) (3,17,27). In light of the potential utility of this agent for the therapy of CAPD peritonitis (2, 10, 16), this study was designed to characterize the pharmacokinetics of teicoplanin after single-dose intravenous (i.v.) and intraperitoneal (i.p.) administration to subjects undergoing CAPD therapy.Five CAPD patients gave informed written consent to participate in this study. The study was approved by the Human Subjects Research Committee, Hennepin County Medical Center. None of the patients had a history of true hypersensitivity to vancomycin, peritonitis within 1 month before study participation, documented hearing loss or abnormal vestibular function, or were morbidly obese (>200o of ideal body weight), pregnant, or lactating.Patients maintained their usual CAPD regimen (1-, 1.5-, or 2-liter exchanges of 1.5, 2.5, or 4.25% glucose; Dianeal; * Corresponding author.Baxter-Travenol, Deerfield, Ill.) during participation. Fill and drainage times were approximately 15 min each in all study subjects. After the initial 24 h of each study phase, dwell times ranged from 4 to 12 hours, depending on the individual dialysis prescription.All patients received a 6-mg/kg 30-min i.v. infusion of teicoplanin and an i.p. instillation of 6 mg/kg in the first dialysate exchange of the day. The order of study phases was randomly assigned, and an 8-week washout period separated the study phases.Blood samples of 5 ml were obtained just before initiation, at the midpoint, at the end of the i.v. infusion-i.p. instillation, and at 15, 30, and 45 min and 1, 2, 3, 4, 5, 6, 8, 12, and 24 h after the end of the infusion-instillation. In addition, blood samples were obtained 48, 72, 96, 120, 168, and 216 h after the infusion-instillation and then once weekly for 7 additional weeks.Dialysate was collected immediately predose and 0, 15, and 30 min and 1, 2, 3, 4, and 6 h after the end of the infusion-instillation (using a three-way stopcock inserted into the CA...

An Open, Randomized, Single-Center, Crossover Pharmacokinetic Study of Meropenem after Intraperitoneal and Intravenous Administration in Patients Receiving Automated Peritoneal Dialysis

“…drug exposure (Table 3). These results are in good agreement with data for other antibiotics, such as fosfomycin, cefotaxime, teicoplanin, vancomycin, and aminoglycosides (3,12,13).…”

Pharmacokinetics of Teicoplanin in Patients Undergoing Continuous Ambulatory Peritoneal Dialysis

“…However, concentrations of teicoplanin in the dialysate 48hours after its administration remained significantly below the therapeutic range [Figure1(b)]. In other studies, teicoplanin was administered intravenously at doses of 3and 6mg/kg in patients on C APD (12)(13)(14). In those studies, the achieved serum levels were significantly lower than those of the present study, whereas detected concentrations of teicoplanin in the dialysate were below 1 µg/mL.…”

“…Teicoplanin has been administered both intravenously and intraperitoneally in anuric patients undergoing CAPD, but at dose regimens not achieving serum concentrations within the therapeutic range (11)(12)(13)(14). The present study was designed to evaluate the pharmacokinetics of teicoplanin after a single intravenous dose higher than those already applied in patients on CAPD.…”

“…Teicoplanin has been shown to be effective after intraperitoneal administration for the treatment of peritonitis in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) (7-10); however, pharmacokinetic data of its intravenous administration in patients undergoing CAPD are limited. Studies performed so far comprised only a limited number of patients in whom teicoplanin was administered intravenously at single doses of 3and 6mg/kg (11)(12)(13)(14), without, however, achieving the ideal therapeutic range in either serum or peritoneal fluid. In order to evaluate whether a larger intravenous dose of teicoplanin might produce the desired therapeutic concentrations, the pharmacokinetics of a single intravenous 10-mg/kg dose of teicoplanin was studied in anuric patients on CAPD.…”

Therapeutic Drug Level Monitoring of Teicoplanin in Korean Pediatric Patients with Normal versus Impaired Renal Function

“… 28 29 Previous studies were mostly confined to adult population with various settings of renal replacement therapy since the early era of teicoplanin. 30 31 32 33 34 In those studies, adult patients with renal failure tended to have prolonged half-life and reduced total body clearance of teicoplanin, while volume of distribution varied. Lam et al 35 have suggested a nomogram for dosage adjustment in adults with varying degrees of renal failure.…”