E Lamont (1), AH Thomson (2,3), M Dawber (2), L Semple (4), E Bell (4), RA Seaton (4)
1 Pharmacy Dept, Gartnavel General Hospital, 2 Pharmacy Dept, Western Infirmary, 3 CAMS Division, University of Glasgow, 4 Brownlee Centre, Gartnavel General Hospital, Glasgow
Introduction. The Outpatient Home Parenteral Antibiotic Therapy (OHPAT) service has been developed to manage infections in patients who require intravenous antibiotic therapy but do not require hospitalisation. Teicoplanin is a glycopeptide antibiotic with a long elimination half-life, which makes it ideal for outpatient use. Currently, it is administered three times per week but there are no established guidelines for the optimal dosage regimen to use in this setting.
Objectives. The aims of this study were to determine the population pharmacokinetics of teicoplanin from routine data collected from the OHPAT clinic and to develop dosage guidelines for clinical use.
Methods. Patients received loading doses of 15 – 25 mg/kg/day for three days followed by 15 – 25 mg/kg on Mondays, Wednesdays and Fridays. Teicoplanin concentrations were measured once weekly on Mondays and the dose was adjusted to maintain troughs of 20–30 mg/litre (deep seated infections) or 10-20 mg/litre (bacteraemia or cellulites). Population pharmacokinetic analysis was performed using NONMEM with FOCE interaction. One and two compartment structural models and additive, proportional and combined error models were compared. The following clinical factors were investigated for their influence on teicoplanin pharmacokinetics: age; sex; teicoplanin dose; albumin concentration; total body weight (TBW); ideal body weight (IBW); height; serum creatinine concentration. Creatinine clearance (CrCL) estimates obtained using the Cockcroft Gault (CG) equation [1] with TBW (CrCLCGT), the CG equation with IBW (CrCLCGI) and the Salazar Corcoran (CrCLSC) equation [2] were also evaluated.
Results. The data set comprised 93 patients whose ages ranged from 15 to 94 years and weights from 43 to 146 kg. Fifty percent of the patients were >20% above their ideal body weights. Estimated CrCLCGT ranged from 17 to 195 (median 65) ml/min There were 471 teicoplanin concentrations ranging from 6.7 to 58.3 mg/L. The data were adequately described by a one-compartment model with proportional residual error. Preliminary covariate analyses identified a relationship between CL and CrCLCGT i.e. CL (L/h) = 0.533 x (1 + 0.01 x (CrCLCGT –65)) and had an IIV of 22%. Volume (L) = 95 x (1 + 0.00597 x (weight – 72)) with an IIV of 38%. Residual error had a cv of 13%.
Conclusions. This study has established a model to describe the pharmacokinetics of teicoplanin in OHPAT patients receiving 15 – 25 mg/kg three times a week. The model will be used to develop dosage guidelines to achieve target concentrations for this group of patients.
References
1. Cockcroft DW and Gault H. Nephron 1976; 16: 31-41.
2. Salazar D and Corcoran G. Am J Med 1988; 84:1053-1060.
Reference: PAGE 13 () Abstr 481 [www.page-meeting.org/?abstract=481]
Poster: poster