Pharmacokinetics of teicoplanin upon multiple dose intravenous administration to normal healthy male volunteers.
Teicoplanin pharmacokinetics were investigated upon multiple dose intravenous administration of 6 and 12 mg kg-1 in 10 normal, healthy, male volunteers, using a two-period, randomized, crossover design; six subjects completed both periods. On day 1, 6 or 12 mg kg-1 was administered every 12 h as a 30-min constant rate intravenous infusion (two doses). Starting on day 2, the same dose (6 or 12 mg kg-1) was administered every 24 h for an additional 13 days. Blood and urine samples were collected over 21 days. Serum and urine were analyzed using a microbiological assay. Following a minimum of 3 weeks after completion of the first period, subjects were crossed over to the other dose. Following multiple dose intravenous administration of 6 and 12 mg kg-1, median pharmacokinetic parameters included: steady-state volume of distribution of 1.4 and 1.2 l kg-1; total clearance of 12.2 and 14.0 ml h-1 kg-1; renal clearance of 11.1 and 10.3 ml h-1 kg-1; and terminal disposition half-life of 159 and 155 h, respectively. No statistically significant dose-related difference was observed. In addition, a cross-study comparison further supports dose proportionality of teicoplanin upon multiple dose intravenous administration of 3 to 12 mg kg-1.
Thompson
G A
GA
Marion Merrell Dow Inc., Cincinnati, OH 45215.
Smithers
J A
JA
Kenny
M T
MT
Dulworth
J K
JK
Kulmala
H K
HK
Yuh
L
L
Lewis
E W
EW
Antony
K K
KK
D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D006020:Glycopeptides / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D011897:Random Allocation; D017334:Teicoplanin
D000900:Anti-Bacterial Agents; D006020:Glycopeptides; D017334:Teicoplanin