Abstracts

Lamotrigine (LTG) is an anticonvulsant commonly used in childhood epilepsy. Drawbacks to therapeutic drug monitoring of LTG (and other drugs) utilizing blood tests include fear and pain to the child, costs, and the use of sharps. Saliva sampling represents a painless and cheaper method of evaluating the concentration of drug in the body, contingent upon reliable reflection of plasma concentration of drug. It has been previously assessed for a large number of anticonvulsants. Studies of salivary LTG disposition to date have focussed on adults or mixed pediatric/adult popualtions.
Our objectives were to 1) Explore the utility of saliva for therapeutic drug monitoring of LTG in epileptic children. 2) To explore the effects of stimulation of salivary flow on the measured concentration of LTG. Children with epilepsy who were on LTG therapy were recruited from the Royal Children[apos]s Hospital, Brisbane, Australia. Approval for the study was obtained from the hospital[apos]s ethics committee. A minimum of 1 mL of saliva was obtained by simple expectoration, or by gentle pippette suctioning of the mouth, and was collected at rest and following stimulation by chewing a small piece of Teflon. A single blood sample was taken between the salivary collections. The volume of saliva and time for collection was noted. The caregivers rating of salivary collection as a testing method was also recorded. Saliva and plasma samples were analyzed for LTG using a validated HPLC method. Statistical analysis was performed using 1-way ANOVA. Twenty-two children (age range 1-16 years) participated; two failed to complete testing. A large range in salivary/plasma (S/P) LTG ratios was noted in both stimulated (range 0.34-0.58) and unstimulated (0.36-0.57) groups. No significant differences were found between stimulated and unstimulated S/P ratios (paired samples mean difference=0.01), nor in stimulated (p=0.12) or unstimulated (p=0.42) salivary LTG levels across the range of plasma LTG concentrations (4.8-18.4 ug/mL). No differences relating to patient age or the time of last dose were noted. Average parental rating (out of 5) for the salivary collection was 4.1 (min 3, max 5). Saliva sampling is a convenient method of monitoring LTG in children, is acceptable to parents, and is not dependant on stimulation techniques. Further studies should confirm that S/P ratios are consistent and reproducible for an individual. More frequent sampling could thus be facilitated at times of breakthrough seizures, altered pharmacokinetics (e.g puberty), and in remote settings where collection facilities are limited. This study also adds to the relatively small volume of knowledge regarding drug disposition in the pediatric population. (Supported by RCH foundation, Cressbrook Committee, and Golden Casket Queensland.)