Influence of Pantoprazole Dosages on Azole Plasma Concentrations in Lung Transplant Recipients

The aim of this observation was to investigate the effect of concomitant therapy with pantoprazole [PPZ] on azole plasma trough levels [APL] of patients following lung transplantation [LTx]. Between July 2013 and July 2014 180 APL of 61 lung transplant recipients [LTR; 32 male, age 57.5±9.5 years, time since LTx 1.6±1.8 years, underlying disease: lung fibrosis (n=30; 49%), chronic obstructive pulmonary disease (n=27; 44%), pulmonary hypertension (n=4; 7%)] receiving either 200mg itraconazole [ITR], 200mg voriconazole [VOR] or 400mg posaconazole [POS] twice daily as well as PPZ were evaluated. The target plasma levels [TPL] of azoles were defined as follows: ITR and POS >700µg/L, VOR >1000µg/L. Standard immunosuppression consisted of tacrolimus, mycophenolate mofetil and steroids. APL were assessed using high performance liquid chromatography. Descriptive analysis was performed. Statistical analysis was carried out using chi-square test. 122 (68%) APL were measured with 40mg PPZ, 58 (32%) with 80mg. 2.7±2.6 APL were measured per patient (ITR 2.6±1.9; VOR 2.5±1.6; POS 2.8±4.2). The mean APL for ITR, VOR and POS measured along with PPZ are shown in table 1. With 40mg PPZ dosage 66% (n=80) of the APL reached the TPL (ITR n=39, 66%; VOR n=18, 62%; POS n=23, 68%), with 80mg PPZ 50% (n=29) reached the TPL (ITR n=14, 56%; VOR n=11, 48%; POS n=4, 40%). For the 80mg dosage significant less APL achieved the TPL (p=0,026). Especially 80mg PPZ did show an impact on the achieved APL with POS APL under TPL. Therapeutic drug monitoring for APL should be part of best practice management following lung transplantation. The influence of PPI on POS APL merits further investigation.