title: Therapeutic drug monitoring of tobramycin: once-daily versus twice-daily dosage schedules.
abstract: OBJECTIVE
  To evaluate the effect of dosage regimen (once-daily vs. twice-daily) of tobramicyn on steady-state serum concentrations and toxicity.
  
  
  METHODS
  Patients undergoing treatment with i.v. tobramycin (4 mg/kg/day) were randomised to two groups. Group OD (n = 22) received a once-daily dose of tobramycin and group TD (n = 21) received the same dose divided into two doses daily. Tobramycin serum concentrations (peak and trough) were measured by enzyme multiplied immunoassay. The renal and auditory functions of the patients were monitored before, during and immediately after treatment.
  
  
  RESULTS
  The two groups were comparable with respect to sex, age, body weight and renal function. No statistically significant differences were found in mean daily dose, duration of treatment, or cumulative dose. Trough concentrations were < 2 g/ml in the two groups (100%). Peak concentrations were > 6 microg/ml in 100% of the OD group and in 67% of the TD group (P< 0.01). Mean peak concentrations were markedly different: 11.00+/-2.89 microg/ml in OD vs. 6.53+/-1.45 microg/ml in TD (P< 0.01). The pharmacokinetics parameters were: Ke, (0.15+/-0.03/h in OD vs. 0.24+/-0.06/h in TD), t1/2, (4.95+/-1.41 h in OD vs. 3.07+/-0.71 h in TD), Vd (0.35+/-0.11 l/kg in OD vs. 0.33+/-0.09 l/kg in TD), Cl (0.86+/-0.29 ml/min/kg in OD vs. 1.28+/-0.33 ml/min/kg in TD). Increased serum creatinine was observed in 73% of patients in OD versus 57% of patients in TD, without evidence of nephrotoxicity. In TD group, three patients developed decreased auditory function, of which one presented with an auditory loss of -30 dB, whereas in the OD group only one patient presented decreased auditory function.
  
  
  CONCLUSIONS
  This small study suggests that a once-daily dosing regimen of tobramycin is at least as effective as and is no more and possibly less toxic than the twice-daily regimen. Using a single-dose therapy, peak concentration determination is not necessary, only trough samples should be monitored to ensure levels below 2 microg/ml.
authors.affiliation: Department of Pharmacy, Arnau de Vilanova Hospital, Valencia, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Sánchez-Alcaraz
authors.forename: A
authors.initials: A
authors.lastname: Vargas
authors.forename: M B
authors.initials: MB
authors.lastname: Quintana
authors.forename: A
authors.initials: A
authors.lastname: Rocher
authors.forename: J M
authors.initials: JM
authors.lastname: Querol
authors.forename: J L
authors.initials: JL
authors.lastname: Poveda
authors.forename: M
authors.initials: M
authors.lastname: Hermenegildo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D003404:Creatinine / Q000097:blood; D004334:Drug Administration Schedule; D016903:Drug Monitoring; D005260:Female; D034381:Hearing Loss / Q000139:chemically induced*; D006801:Humans; D007668:Kidney / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D014031:Tobramycin / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood
chemical_list: D000900:Anti-Bacterial Agents; D003404:Creatinine; D014031:Tobramycin