Teicoplanin pharmacokinetics in healthy volunteers after administration of intravenous loading and maintenance doses

Abstract

Teicoplanin is an investigational glycopeptide antibiotic that is structurally and microbiologically similar to vancomycin. Since teicoplanin possesses a very long elimination half-life, the manufacturer suggests that the drug be administered every 12 h for the first day of therapy and once daily thereafter. We studied the multiple-dose (6 mg/kg per dose) pharmacokinetics of teicoplanin in volunteers following intravenous administration every 12 h for 5 days and then every 24 h for 9 days in an attempt to identify the optimal duration of the every-12-h loading-dose regimen. Multiple serum samples were obtained throughout the study, including intensive sampling after the first and last doses; urine was collected during the entire study. A three-exponential equation was fitted to the serum concentration data. The mean terminal-phase half-life was 157 +/- 93 h. Concentrations of teicoplanin in serum similar to those observed after the administration of the last dose (day 14) were observed following the fourth or fifth dose given every 12 h. Therefore, it is suggested that for clinical dosing regimens for teicoplanin, dosing every 12 h for approximately 48 h should be used, followed by once-daily dosing thereafter.

Pharmacokinetics of teicoplanin upon multiple-dose intravenous administration of 3, 12, and 30 milligrams per kilogram of body weight to healthy male volunteers

“…Results from previous studies conducted with normal healthy volunteers indicate that the pharmacokinetics of teicoplanin upon multiple-dose intravenous administration are linear over the range of 3 to 12 mg/kg (11,14,21). In the present study, the pharmacokinetics of teicoplanin upon Results of the present study indicate that teicoplanin total and renal clearances are independent of dose and that total clearance is determined primarily by renal clearance.…”

“…As a result of the increase in the duration of sample collection, teicoplanin total clearance was found to be slightly less and the volumes of distribution and terminal disposition half-life were found to be greater than previously reported. Results from these more recent studies indicate that the pharmacokinetics of teicoplanin upon multiple-dose intravenous administration are linear over the range of 3 to 12 mg/kg of body weight (11,14,21 predominantly by renal clearance and that dosage adjustments may be necessary for patients with impaired renal function.As a result of a recent increase in the dose being used in clinical investigations, this study was undertaken to evaluate the pharmacokinetics of teicoplanin upon multiple-dose intravenous administration of 3, 12, and 30 mg/kg to healthy volunteers. …”

“…As a result of the increase in the duration of sample collection, teicoplanin total clearance was found to be slightly less and the volumes of distribution and terminal disposition half-life were found to be greater than previously reported. Results from these more recent studies indicate that the pharmacokinetics of teicoplanin upon multiple-dose intravenous administration are linear over the range of 3 to 12 mg/kg of body weight (11,14,21). Over this range of doses, teicoplanin pharmacokinetics are characterized by the following median parameters: total clearance of 13.1 ml/h/kg, renal clearance of 10.8 mlIh/kg, steady-state volume of distribution of 1.2 liters/kg, and a terminal disposition half-life of 157 h. These results indicate that total clearance is determined * Corresponding author.…”

“…A review of these studies has recently been published (16). In more recent studies, the duration of sample collection has been extended up to 3 weeks, resulting in a more complete characterization of the serum concentration-time profile (1,11,14,21). As a result of the increase in the duration of sample collection, teicoplanin total clearance was found to be slightly less and the volumes of distribution and terminal disposition half-life were found to be greater than previously reported.…”

Right-sided endocarditis caused by Staphylococcus aureus in drug abusers

“…Because of the poor results reported with dosages lower than 6 mg/kg/day, dosages of 20 mg/kg/day for the first 3 days and 12 mg/kg/day for the next 4 days were used. Because of the reported cumulative effect of teicoplanin (3,19), the dosage after the 8th day was decreased to 7 mg/kg/day. This cumulative effect was not observed in the present study.…”