Actinomycin D is an anti-tumour antibiotic used
routinely to treat certain forms of cancer and is an
important component of chemotherapies used during
bone marrow transplantation. The mechanism of action of actinomycin D is thought to involve its
intercalation with DNA, i.e. insertion into the DNA
helix, and the subsequent inhibition of DNA transcription.
This results in inhibition of RNA synthesis
and, secondarily, protein synthesis [1,2]. Actinomycin
D can also form single-strand DNA breaks
through inhibition of topoisomerase II, a nuclear
enzyme essential for cell replication due to its ability
to create and reseal breaks in double-stranded
DNA [3]. Actinomycin D is currently used to treat a
number of paediatric malignancies, including Wilms’
tumour, Ewing’s sarcoma and rhabdomyosarcoma
[4–6].
Despite its long history of clinical use, the pharmacokinetics
of actinomycin D in humans have been the
subject of a very limited number of studies in adults
[7,8], and no reported studies in children. This compares
strikingly with chemotherapeutic agents such as
etoposide and carboplatin, which have been the subject
of numerous pharmacokinetic studies in various
patient populations [9–12]. The importance of these
studies is best exemplified by carboplatin, whereby results
from clinical pharmacokinetic studies have been
used successfully to guide patient treatment.