Comparable aciclovir exposures produced by oral valaciclovir and intravenous aciclovir in immunocompromised cancer patients

The objective of this study was to evaluate the comparability of systemic a ciclovir exposure at steady state in immunocompromised patients following o ral valaciclovir 1000 mg tds and intravenous (iv) aciclovir 5 mg/kg tds. A two-centre, randomized, open label, two-way crossover study was undertaken. Patients aged 18-65 years who had undergone high-dose chemotherapy for can cer and were neutropenic (neutrophil count <0.5 x 10(9)/mL) with normal ren al function were recruited. The pharmacokinetic parameters of aciclovir aft er oral valaciclovir 1000 mg or iv aciclovir 5 mg/kg given as 1 h infusion, each administered every 8 h for seven doses, were compared. Fifteen patien ts were enrolled and 13 completed both treatments. The mean (S.D.) values f or aciclovir after oral valaciclovir and iv aciclovir were: AUC(0-8) 76.3 ( 29.7) and 64.2 (20.0) muM-h; peak plasma concentration (C-max) 26.6 (10.5) and 34.0 (11.9) muM; time to maximal plasma concentration (t(max)) 2.01 (0. 65) and 0.95 (0.19); and plasma elimination half-life (t(1/2)) 2.83 (0.91) and 2.44 (0.62) h, respectively. The mean absolute bioavailability of acicl ovir from oral valaciclovir was 60 +/- 21%. Equivalent systemic exposure to aciclovir after oral valaciclovir 1000 mg and iv aciclovir 5 mg/kg was obs erved with AUC(0-8) (oral/iv ratio 1.16; 90% CI 0.98-1.39), whilst signific antly reduced peak aciclovir concentrations were obtained with oral valacic lovir (ratio = 0.75; 90% CI 0.60-0.94). Oral valaciclovir offers a convenie nt, and possibly safer, alternative to iv aciclovir, delivering comparable systemic exposures with reduced peak levels. This may contribute to shorter hospitalization, reduced costs for healthcare providers and improved quali ty of life for patients.