Clinical Pharmacokinetics

, Volume 43, Issue 6, pp 405–415 | Cite as

Teicoplanin in Patients with Acute Leukaemia and Febrile Neutropenia

A Special Population Benefiting from Higher Dosages
  • Federico Pea
  • Pierluigi Viale
  • Anna Candoni
  • Federica Pavan
  • Leonardo Pagani
  • Daniela Damiani
  • Marco Casini
  • Mario Furlanut
Original Research Article

Abstract

Objective

To define the optimal dosage regimen of teicoplanin that ensures early therapeutically relevant trough concentrations (Cmin) [>10 mg/L at 24 hours and possibly close to 20 mg/L at 48 hours] in patients with acute leukaemia who develop febrile neutropenia after chemotherapy.

Design

Prospective observational pharmacokinetic study.

Participants

Adult patients (n = 33) with normal renal function previously treated with antineoplastic chemotherapy because of acute lymphocytic or acute nonlymphocytic leukaemia, and subsequently developing febrile neutropenia treated with empirical antimicrobial therapy.

Design

First, the standard dosage group (n= 11) was administered standard loading and maintenance doses of teicoplanin (400mg every 12 hours for three doses followed by 400mg once daily). Blood samples were collected at defined times as part of routine monitoring and assessed for teicoplanin plasma concentration by fluorescence polarisation immunoassay. Secondly, the high dosage group (n = 22) received a high loading regimen (800 + 400mg 12 hours apart on day 1, 600 + 400mg 12 hours apart on day 2) followed by a high maintenance regimen (400mg every 12 hours) from day 3 on.

Results

In the standard dosage group, no patient had the recommended teicoplanin Cmin of ≥10 mg/L within the first 72 hours, and only five of the 11 patients (45%) had a Cmin of ≥10 mg/L after 120 hours. No patient had a Cmin of ≥20 mg/L. In the high dosage group, teicoplanin Cmin averaged ≥10 mg/L within 24 hours, and this value was achieved within 48 hours in all but one patient. Of note, Cmin at 72 hours exceeded 20 mg/L in ten of the 22 patients (45%). No patient experienced significant impairment of renal function.

Conclusions

In this patient group, therapeutically relevant Cmin may be achieved very early in the treatment period with loading doses of 12 mg/kg and 6 mg/kg 12 hours apart on day 1, and 9 mg/kg and 6 mg/kg 12 hours apart on day 2, regardless of renal function. Subsequently, in patients with normal renal function a maintenance dosage of 6 mg/kg every 12 hours may be helpful in ensuring Cmin close to 20 mg/L. Assessment of Cmin after 48–72 hours may be useful to individualise teicoplanin therapy. Factors increasing volume of distribution and/or renal clearance of teicoplanin (fluid load, hypoalbuminaemia, leukaemic status) may explain the need for higher dosages.

Keywords

Therapeutic Drug Monitoring Normal Renal Function Teicoplanin Acute Leukaemia High Dosage Group 

Notes

Acknowledgements

The authors have provided no information on sources of funding or on conflicts of interest directly relevant to the content of this study.

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Copyright information

© Adis Data Information BV 2004

Authors and Affiliations

  • Federico Pea
    • 1
  • Pierluigi Viale
    • 2
  • Anna Candoni
    • 3
  • Federica Pavan
    • 1
  • Leonardo Pagani
    • 4
  • Daniela Damiani
    • 3
  • Marco Casini
    • 5
  • Mario Furlanut
    • 1
  1. 1.Department of Experimental and Clinical Pathology and Medicine, Medical School, Institute of Clinical Pharmacology and ToxicologyUniversity of UdineUdineItaly
  2. 2.Department of Medical and Morphological Research, Medical School, Clinic of Infectious DiseasesUniversity of UdineUdineItaly
  3. 3.Department of Medical and Morphologic Research, and Division of Hematology, Medical School, Chair of HematologyUniversity of UdineUdineItaly
  4. 4.Division of Infectious DiseasesBolzano General HospitalBolzanoItaly
  5. 5.Division of HematologyBolzano General HospitalBolzanoItaly

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