Variability in Trough Total and Unbound Teicoplanin Concentrations and Achievement of Therapeutic Drug Monitoring Targets in Adult Patients with Hematological Malignancy.
The objective of this study was to explore the following aspects of teicoplanin use in patients with hematological malignancy: early attainment of target trough concentrations with current high-dose teicoplanin regimens, variability in unbound teicoplanin fractions, factors associated with observed total and unbound trough concentrations, efficacy and toxicity, and renal function estimation. This was a single-center, prospective study. Samples for determination of trough concentrations were taken on days 3, 4, 7, and 10. Total and unbound teicoplanin concentrations were determined using validated high-performance liquid chromatography methods. Regression analyses were used to identify the factors associated with the trough concentration. Thirty teicoplanin-treated adults with hematological malignancy were recruited. Despite the use of dosages higher than the conventional dosages, the proportions of patients with a trough concentration of ≥20 mg/liter at 48 h and at 72 h were 16.7% and 37.9%, respectively. Renal function was significantly negatively associated with total trough concentrations at 48 h and 72 h (P< 0.05). For an average hematological malignancy patient (creatinine clearance = 70 ml/min), sequential loading doses of at least 12 mg/kg of body weight may be needed to achieve early adequate exposure. In the absence of measured creatinine clearance, estimates obtained using the Cockcroft-Gault (total body weight) equation could prove to be an acceptable surrogate. The unbound fractions of teicoplanin were highly variable (3.4 to 18.8%). Higher unbound fractions were observed in patients with low serum albumin concentrations. Teicoplanin was well tolerated. Teicoplanin loading doses higher than those in current use appear to be necessary. Increased dosing is needed in patients with increased renal function. The high variability in protein binding supports the contention for therapeutic drug monitoring of unbound teicoplanin concentrations. (This study has been registered with EudraCT under registration no. 2013-004535-72.).
School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin, Ireland.
Catherine J
CJ
Byrne
Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Australia.|Centre for Translational Anti-Infective Pharmacodynamics, The University of Queensland, Brisbane, Australia.
Jason A
JA
Roberts
Queensland Pathology, Brisbane, Australia.
Brett
B
McWhinney
Tallaght Hospital, Dublin, Ireland.
Jerome P
JP
Fennell
Tallaght Hospital, Dublin, Ireland.
Philomena
P
O'Byrne
Tallaght Hospital, Dublin, Ireland.
Evelyn
E
Deasy
Tallaght Hospital, Dublin, Ireland.
Sean
S
Egan
Tallaght Hospital, Dublin, Ireland.
Ronan
R
Desmond
Tallaght Hospital, Dublin, Ireland.
Helen
H
Enright
School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin, Ireland sryder@tcd.ie.
Sheila A
0000-0002-1396-8905
SA
Ryder
School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin, Ireland.
Deirdre M
DM
D'Arcy
Tallaght Hospital, Dublin, Ireland.
Johnny
J
McHugh
D000368:Aged; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D019337:Hematologic Neoplasms / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D007677:Kidney Function Tests; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D011485:Protein Binding; D012709:Serum Albumin / Q000378:metabolism; D017334:Teicoplanin / Q000009:adverse effects / Q000627:therapeutic use*
D000900:Anti-Bacterial Agents; D012709:Serum Albumin; D017334:Teicoplanin
hematological malignancy; pharmacokinetics; protein binding; teicoplanin; therapeutic drug monitoring