Ticarcillin-clavulanic acid pharmacokinetics in preterm neonates with presumed sepsis.
The objective of the reported study was to characterize the pharmacokinetics of ticarcillin and clavulanic acid in premature low-birth-weight (less than 2,200 g) neonates with presumed sepsis. Eleven infants received 12 courses of ticarcillin-clavulanic acid at 75 mg/kg of body weight intravenously every 12 h. Blood samples were collected at 0.5, 1.5, 4, and 8 h following the infusion of the initial dose. The concentrations of ticarcillin and clavulanic acid were determined by a microbiologic assay. Median (interpatient coefficients of variation) values for the volume of the central compartment, total steady-state volume, distributional clearance, total clearance, and terminal elimination half-life for ticarcillin were 0.030 liter/kg (21%), 0.26 liter/kg (48%), 0.41 liter/h/kg (47%), 0.047 liter/h/kg (47%), and 4.2 h (45%), respectively. For clavulanic acid the parameters were 0.28 liter/kg (32%), 0.36 liter/kg (34%), 11 liters/h/kg (36%), 0.12 liters/h/kg (72%), and 1.95 h (40%), respectively. Our results suggest that the current dosing recommendations of 75 mg/kg every 12 h risk subtherapeutic clavulanic acid concentrations and that 50 mg/kg every 6 h is a more rational dosing strategy.
Burstein
A H
AH
Division of Neuropharmacology, Dent Neurologic Institute, Millard Fillmore Hospital, Buffalo, New York 14209.
Wyble
L E
LE
Gal
P
P
Diaz
P R
PR
Ransom
J L
JL
Carlos
R Q
RQ
Forrest
A
A
D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics; D001825:Body Fluid Compartments; D019818:Clavulanic Acid; D002969:Clavulanic Acids / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007230:Infant, Low Birth Weight / Q000378:metabolism; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000188:drug therapy / Q000378:metabolism*; D007262:Infusions, Intravenous; D008297:Male; D008954:Models, Biological; D018805:Sepsis / Q000188:drug therapy / Q000378:metabolism*; D013982:Ticarcillin / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D065093:beta-Lactamase Inhibitors
D000900:Anti-Bacterial Agents; D002969:Clavulanic Acids; D065093:beta-Lactamase Inhibitors; D019818:Clavulanic Acid; C043215:ticarcillin-clavulanic acid; D013982:Ticarcillin