Effect of Duration and Intensity of Ganciclovir Exposure on Lymphoblastoid Cell Toxicity

Abstract

Introduction: Human cytomegalovirus infection is still a major complication after pediatric bone marrow transplantation and could be fatal in some cases. The toxicity of the drug in dividing transplanted haematopoietic cells combined with the suppression of cell growth caused by the virus remains a major problem in managing human cytomegalovirus infection. Methods: The aim of the current in vitro study was to evaluate the effect of the intensity (1–20 mg/l) and duration (1, 2, 7 or 14 days) of ganciclovir exposure on toxicity in B lymphoblastoid cells (using cell counting and viability measurements). Results: A correlation was found between the dose of ganciclovir exposure and a decrease in total cell number when duration exceeded 2 days (r2=0.92 and 0.93 after 7 and 14 days, respectively). High levels (20 mg/l) of ganciclovir were not more toxic than lowest levels (1 mg/l) for the shortest durations of ganciclovir exposure (1 and 2 days). Moreover, 50% cytotoxic concentrations markedly decreased with the duration of ganciclovir exposure (374–3 mg/l from 1 to 14 days respectively) after 14 days of culture. Conclusions: This in vitro study demonstrated for the first time that ganciclovir exhibited an in vitro duration-dependent toxicity on haematopoietic-derived cells when in vivo doses of the drug were used.