Pharmacokinetic assessment of oral ganciclovir in lung transplant recipients with cystic fibrosis

Oral ganciclovir has been used as prophylaxis and therapy against cytomegal ovirus in patients with HIV infection and following organ transplantation. Oral ganciclovir has clear practical advantages over intravenous ganciclovi r but has a relatively low bioavailability and this may be problematic in a t-risk patients with malabsorption. The bioavailability and therefore thera peutic potential of oral ganciclovir in cystic fibrosis (CF) patients post- lung transplant (LT) might be expected to be inadequate given the high inci dence of malabsorption in these patients. An 8 h pharmacokinetic study was performed in 12 CF patients 160 +/- 122 days post-transplant who had been t aking 1 g oral ganciclovir tds for 3 days with food (plus normal enzyme sup plements). Mean (range) serum creatinine was 150 mu mol/L (70-280). Blood w as sampled at 0.5, 1, 2, 3, 4, 6 and 8 h post-final dose. Plasma was stored at -20 degrees C and later analysed by highperformance liquid chromatograp hy. Mean peak concentration (C-min) was 4.8 mg/L (0.96-12.8), mean minimum concentration (C-min) was 3.6 mg/L (0.78-11.7) and mean area under the curv e (AUC) was 35.4 mg.8 h/L (8-99). C-max, C-min and AUC correlated significa ntly with one another (P < 0.001) as well as with serum creatinine and crea tinine clearance(P < 0.01). When corrected for alterations in renal functio n, plasma oral ganciclovir levels are as predicted for other transplant pop ulations. Three days of oral ganciclovir results in therapeutically useful plasma drug levels in the CF LT population, despite a background of general malabsorption. C-max, C-min and AUC are highly correlated, allowing for th e possibility of steady-state drug monitoring to confirm that the recommend ed dosing algorithm produces appropriate plasma levels.