JAC Advance Access originally published online on May 2, 2009
Journal of Antimicrobial Chemotherapy 2009 64(1):181-187; doi:10.1093/jac/dkp147
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Original research |
Development of teicoplanin dosage guidelines for patients treated within an outpatient parenteral antibiotic therapy (OPAT) programme
1 Pharmacy Department, Gartnavel General Hospital, NHS Greater Glasgow and Clyde, Glasgow G12 0YN, Scotland, UK 2 Brownlee Centre, Gartnavel General Hospital, NHS Greater Glasgow and Clyde, Glasgow G12 0YN, Scotland, UK 3 Division of Medical Sciences, Western Infirmary University of Glasgow, Glasgow G11 6NT, Scotland, UK 4 Pharmacy Department, Western Infirmary, NHS Greater Glasgow and Clyde, Glasgow G11 6NT, Scotland, UK 5 Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Western Infirmary, Glasgow G4 0NR, Scotland, UK
Received 4 September 2008; returned 2 December 2008; revised 30 March 2009; accepted 2 April 2009
* Corresponding author. Strathclyde Institute of Pharmacy and Biomedical Sciences, John Arbuthnott Building, 27 Taylor Street, Glasgow G4 0NR, Scotland, UK. Tel: +44-0141-548-2506; Fax: +44-0141-552-2562; E-mail: alison.h.thomson{at}strath.ac.uk
Objectives: The long elimination half-life of teicoplanin facilitates outpatient parenteral antibiotic therapy (OPAT) with thrice-weekly dosing. This study aimed to develop teicoplanin dosage guidelines for OPAT use from routine clinical data.
Methods: Patients received 15–25 mg/kg/day for 3 days, then 15–25 mg/kg thrice weekly. Trough concentrations were measured weekly and doses adjusted to maintain 20–30 or 10–20 mg/L according to clinical condition. Concentration–time data were analysed using the pharmacokinetic package NONMEM and the final model was used to develop new dosage guidelines.
Results: Data from 94 and 36 patients were used for model development and validation, respectively. Patient ages ranged from 15 to 94 years, weights from 43 to 146 kg and estimated CLCR from 9 to 195 mL/min. Teicoplanin concentrations (n = 670) ranged from 6.7 to 66.9 mg/L and a one-compartment model adequately described the data. The typical estimate of CL was 0.542 L/h and changed by 10.6% for every 10 mL/min difference from a CLCR of 66 mL/min. V was 1.62 L/kg. Dosage guidelines based on body weight and CLCR can be expected to lead to a significant improvement in the proportion of concentrations in the range 20–30 mg/L. Alternative doses aimed at lower target concentrations have also been developed.
Conclusions: New dosage guidelines have been developed to support thrice-weekly administration of teicoplanin in an OPAT setting.
Keywords: population pharmacokinetics , therapeutic drug monitoring , extended interval dosing
Present address: Clinical Development, Medical Science, AstraZeneca, Alderley Park, Macclesfield, Cheshire, UK.