Randomized comparison of serum teicoplanin concentrations following daily or alternate daily dosing in healthy adults.
Trough serum teicoplanin concentrations were compared in healthy adults following intravenous administration of one of two regimens: (i) 12 mg/kg of body weight every 12 h for 3 doses and then 15 mg/kg every 48 h for 4 doses (n = 16 subjects) or (ii) 6 mg/kg every 12 h for 2 doses and then 6 mg/kg every 24 h for 9 doses (n = 8 subjects). The mean +/- standard deviation trough concentrations in serum on day 11 (24 and 48 h after administration of the last dose for the daily and alternate-day dosing schedules, respectively) were 16.0 +/- 2.1 and 17.9 +/- 3.5 mg/liter for subjects receiving the two regimens, respectively, by a fluorescence polarization immunoassay. The limits of the 95% confidence interval of the difference (-0.2, 3.6 mg/liter) determined by a nonparametric test were situated above the -1.3-mg/liter maximum set difference and indicated a noninferiority of the alternate-day dosing to the daily dosing. Throughout the study the individual trough concentrations in serum in the alternate-day dosing group constantly exceeded 10 mg/liter, the presently recommended target concentration for the treatment of severe infections. The trough concentrations in the sera of all subjects were bactericidal for six Staphylococcus aureus strains for which teicoplanin MICs are between 0.5 and 4 mg/liter. The bactericidal activity of serum was related to total teicoplanin (protein bound and unbound). In conclusion, an alternate-day dosing schedule (15 mg/kg on alternate days following administration of a 12-mg/kg loading dose three times every 12 h) could be considered for further efficacy and safety studies.
Rouveix
Bernard
B
Service de Pharmacologie Clinique, Hôpital Cochin, and ITEC Pharmacology, Paris, France. bernard.rouveix@cch.ap-hop-paris.fr
Jehl
François
F
Drugeon
Henri
H
Brumpt
Ivan
I
Caulin
Evelyne
E
D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood*; D019540:Area Under Curve; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008826:Microbial Sensitivity Tests; D015610:Serum Bactericidal Test; D013211:Staphylococcus aureus / Q000187:drug effects; D017334:Teicoplanin / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood*
D000900:Anti-Bacterial Agents; D017334:Teicoplanin