Posaconazole therapeutic drug monitoring in cystic fibrosis lung transplant patients

Berge M., Guillemain R., Lefeuvre S., Amrein C., Boussaud V., Chevalier P., Dannaoui E., Billaud E.M.

Author address: 

NULL

Abstract: 

Invasive aspergillosis represents a major complication in lung transplantation (LTx) particularly in case of cystic fibrosis (CF). Posaconazole (PSZ) is indicated for the curative and prophylactic treatment of invasive fungal infections using respectively 400mgx2/day and 200mgx3/day doses. PSZ absorption is saturable, therefore dose increase often needed in CF patients is limited. PSZ half life is long (35h), resulting in long time to steady state (SS). Objective: To show that PSZ therapeutic drug monitoring (TDM) in CFLTx allows 1- the achievement of trough concentrations (C0) levels consistent with efficiency (> 0.5 mg/L) or at least detectable (> 0.2 mg/L) ; 2 the management of PSZ metabolic drug interactions with immunosuppressants. Methods: Retrospective and prospective cohort of CFLTx under PSZ between 2006 and 2008 in our center. Longitudinal collection of both doses and C0 (at SS) data for PSZ and immunosuppressants. TDM by determination of plasma PSZ by LC assay with fluorimetric detection. Results: 17 CFLTx , aged 26 ± 8 years, received curative (n = 2), preemptive (n = 14) or prophylactic (n = 1) PSZ treatment. Caspofungin was combined to PSZ in 8 patients. The mean treatment duration was 228 ± 197 days, [14-621]. PSZ introduction corresponded to immediate (n=4), first year (n=5) or beyond (n=8) post Tx. 220 PSZ C0 were analyzed. No post Tx time effect on PSZ exposure was observed. The mean PSZ C0 was 0.7 ± 0.5 mg/L, [0.2;1.6] using an average PSZ dose of 1084 ± 310mg/day, [733;1889], resulting in more than +35% of the recommended dose (p 3mg/L has been observed. PSZ safety profile was good. Indeed, PSZ acted as a moderate CYP3A4 metabolic inhibitor, justifying a joint TDM of both PSZ and immunosuppressants to manage the immunosuppressants dose adjustment at the introduction or discontinuation of PSZ.
2009

abstract No: 

P 1751

Full conference title: 

19th European Congress of Clinical Microbiology and Infectious Diseases
    • ECCMID 19th (2009)