An in vivo assessment of the tobramycin/ticarcillin interaction in cystic fibrosis patients.
A non-blinded, randomized, cross-over investigation of the pharmacokinetic interaction between tobramycin and ticarcillin was performed in 18 healthy cystic fibrosis (CF) patients with normal renal function. On consecutive mornings the patients were given either tobramycin intravenously (i.v.) over 3-5 min (TOB phase), or tobramycin i.v. over 3-5 min followed immediately by ticarcillin infused i.v. over 20-30 min (TOB+TIC phase). Capillary blood samples were taken 30 min and 330 min after administration of the tobramycin dose in each phase. Tobramycin was measured in serum by fluorescence polarization immunoassay (TDx). There were decreases in serum tobramycin concentrations of 11% at 30 min (P < 0.001) and 330 min (P = 0.012) when measured in the presence of ticarcillin. No difference in elimination half-life was found (TOB phase 95 +/- 13 min, TOB+TIC phase 95 +/- 13 min, P = 0.86). The volume of distribution and clearance of tobramycin increased by 14% (P < 0.001) and 13% (P < 0.001), respectively, in the presence of ticarcillin. This interaction appears to be of minor clinical importance but pharmacokinetic studies of tobramycin should exclude concurrent use of ticarcillin.
Roberts
G W
GW
Department of Pharmacy, Adelaide Children's Hospital, North Adelaide, 5006, Australia.
Nation
R L
RL
Jarvinen
A O
AO
Martin
A J
AJ
D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000378:metabolism*; D004338:Drug Combinations; D004347:Drug Interactions; D006801:Humans; D007262:Infusions, Intravenous; D010406:Penicillins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013982:Ticarcillin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014031:Tobramycin / Q000008:administration & dosage / Q000493:pharmacokinetics*
D000900:Anti-Bacterial Agents; D004338:Drug Combinations; D010406:Penicillins; D013982:Ticarcillin; D014031:Tobramycin