Ganciclovir treatment in children: evidence of subtherapeutic levels.

Ganciclovir (GCV) is used to treat babies and older children with cytomegalovirus-related disease. Treatment courses are generally derived from adult studies and there are few data relating to the pharmacokinetics of GCV in children. In adults, low trough GCV levels have been associated with treatment failure and virological resistance. Data regarding suitable drug levels for use in therapeutic drug monitoring (TDM) in the paediatric age group do not currently exist. In this study, anonymised data for all GCV levels sent to the UK Antibiotic Reference Laboratory from 1 November 1999 to 31 March 2007 were reviewed and analysed by age group. In total, 339 specimens were received from 129 patients; 192 specimens were from patients aged <18 years. There were significantly more trough GCV levels <0.5 mg/L in those aged <6 months and 6-12 months compared with adults (64.8% and 53.9%, respectively, vs. 15.9%; P<0.001). Those aged 5-18 years also had significantly more trough samples with levels <0.5 mg/L (80.0% vs. 15.9%; P<0.001). There was a significant difference between median peak GCV levels in those aged <6 months and adults (4.8 mg/L vs. 5.7 mg/L, respectively; P=0.047). In conclusion, GCV levels associated with treatment failure and considered subtherapeutic in adult patients were observed more often in specimens from paediatric patients. These lower levels may have implications for dosing in the paediatric age group, particularly during periods of rapid change in renal function such as the neonatal period. Clinicians should be aware of the relatively low drug exposure noted in this study and consider TDM and increasing drug dose where virological response is poor.