Pharmacokinetic profile of voriconazole in a critically Ill patient on therapeutic plasma exchange

BACKGROUND: Extracorporeal removal of drugs during therapeutic plasma exchange (TPE) can lead to decreased efficacy, as shown in several reports discussing altered pharmacokinetics (PKs) of antibiotics during TPE. In particular, drugs with a low volume of distribution or a high protein binding are susceptible to extracorporeal removal, as these drugs remain substantially within the intravascular space. No information is known about antifungal drug removal during TPE. We report the PKs of voriconazole in a critically ill patient undergoing TPE. METHODS: A 61-year-old man, presenting with catastrophic antiphospholipid syndrome for which TPE was started, developed probable pulmonary invasive aspergillosis. Intravenous voriconazole was started. Blood samples were taken under steady state conditions to calculate PK parameters of voriconazole, both with and without TPE. RESULTS: PK parameters (area under the curve, Cl, Vd, and t1/2) were equivalent on both days. Voriconazole has a distribution volume of 4.5 L/kg and a protein binding of 58%, suggesting that drug removal during TPE would not be clinically significant. Our data support this assumption. CONCLUSION: Based on our findings, it seems that TPE does not alter the PK behavior of voriconazole. Voriconazole dosages should not be adjusted during TPE.