title: Pharmacokinetics of teicoplanin upon multiple-dose intravenous administration of 3, 12, and 30 milligrams per kilogram of body weight to healthy male volunteers.
abstract: Teicoplanin pharmacokinetics were evaluated after multiple-dose intravenous administration to healthy male volunteers by using a randomized, double-blind, parallel design. Doses of 3, 12, or 30 mg of teicoplanin per kg of body weight were administered every 24 h for 14 days as 60-min constant-rate intravenous infusions. Blood and urine samples were collected over 21 days and analyzed by a microbiological assay. Twenty-three subjects were included in the pharmacokinetic analysis. The median pharmacokinetic parameters upon multiple-dose intravenous administration of 3, 12, and 30 mg/kg included steady-state volumes of distribution of 0.94, 0.77, and 0.68 liter/kg; total clearances of 11.9, 12.0, and 13.2 ml/h/kg; and terminal disposition half-lives of 143, 166, and 96 h, respectively. Renal clearance accounted for approximately 95% of total clearance. No dose-related differences existed for teicoplanin total or renal clearance. The steady-state volume of distribution decreased significantly with increasing doses. As a result of the decrease in the volume of distribution, the terminal disposition half-life at 30 mg/kg was significantly decreased. However, the decreases in the volume of distribution and terminal disposition half-life are of limited clinical importance, since steady-state trough concentrations in serum increase in proportion to dose. Combined results of all multiple-dose studies with similar durations of sample collection indicate no dose-related differences for any pharmacokinetic parameters from 3 to 12 mg/kg. As observed in the present study, no dose-related differences exist for teicoplanin total and renal clearances from 3 to 30 mg/kg. However, at 30 mg/kg, a significant decrease in the steady-state volume of distribution is observed. As a consequence of the reduction in the volume of distribution at 30 mg/kg with no change in clearance, the terminal disposition half-life is decreased.
authors.affiliation: Marion Merrell Dow Research Institute, Cincinnati, Ohio 45215-6300.
authors.forename: J A
authors.initials: JA
authors.lastname: Smithers
authors.forename: H K
authors.initials: HK
authors.lastname: Kulmala
authors.forename: G A
authors.initials: GA
authors.lastname: Thompson
authors.forename: K K
authors.initials: KK
authors.lastname: Antony
authors.forename: E W
authors.initials: EW
authors.lastname: Lewis
authors.forename: S J
authors.initials: SJ
authors.lastname: Ruberg
authors.forename: M T
authors.initials: MT
authors.lastname: Kenny
authors.forename: J K
authors.initials: JK
authors.lastname: Dulworth
authors.forename: M A
authors.initials: MA
authors.lastname: Brackman
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004311:Double-Blind Method; D006020:Glycopeptides / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D011897:Random Allocation; D017334:Teicoplanin
chemical_list: D000900:Anti-Bacterial Agents; D006020:Glycopeptides; D017334:Teicoplanin