Lamotrigine and therapeutic drug monitoring: retrospective survey following the introduction of a routine service.
OBJECTIVE
To review (retrospectively) the relationships between lamotrigine (LTG) dosage and plasma concentrations based on data generated in a routine therapeutic drug monitoring laboratory from a heterogeneous sample of patients with epilepsy. To distinguish patients taking concomitant anti-epileptic therapy which induced or inhibited drug metabolising enzymes, or a combination of both, together with LTG. To survey medical staff who use a routine LTG assay service with a view to establishing the utility of higher plasma LTG concentrations than those used in early clinical trials.


METHODS
All patient assays for LTG received over a 12 month period (339 requests from 149 patients) were reviewed and relationships between dosage and concentration calculated and grouped according to concomitant antiepileptic drug therapy. The doctors requesting the tests were surveyed by questionnaire (n=40 of 67 responded). They were asked for details about the patient's seizure control, rationale used for LTG dosage adjustment and their acceptance of the proposed 'therapeutic range' adopted by the laboratory of 3-14 mg(-1).


RESULTS
Linear relationships were demonstrated between LTG dosage and concentration for the 3 treatment groups (LTG plus valproic acid (VPA), LTG plus enzyme inducing antiepileptic drugs, and LTG plus VPA and inducers), however, there were significant differences between groups (P<0.001) with a 4.4 fold difference in dosage: concentration ratios between the LTG plus VPA group and the LTG plus inducers group. The questionnaire showed that the therapeutic range was well accepted by 88% of responders, none of whom considered this higher range to be wrong.


CONCLUSIONS
Metabolic inhibition by VPA was shown to have a marked effect on LTG kinetics, suggesting either a significant LTG dosage reduction is required if plasma LTG concentrations are elevated, or alternatively, higher plasma LTG concentrations could be attained from lower dosages. The higher therapeutic range adopted by the laboratory (3-14 mg(-1)) was widely accepted and increasingly applied in clinical practice in the management of patients with epilepsy.
Morris
R G
RG
Department of Clinical Pharmacology, The Queen Elizabeth Hospital, Woodville, South Australia.
Black
A B
AB
Harris
A L
AL
Batty
A B
AB
Sallustio
B C
BC
D000927:Anticonvulsants / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004347:Drug Interactions; D016903:Drug Monitoring / Q000379:methods / Q000706:statistics & numerical data*; D004359:Drug Therapy, Combination; D004827:Epilepsy / Q000188:drug therapy / Q000378:metabolism; D019538:Health Care Surveys; D006801:Humans; D000077213:Lamotrigine; D012189:Retrospective Studies; D014227:Triazines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014635:Valproic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics
D000927:Anticonvulsants; D014227:Triazines; D014635:Valproic Acid; D000077213:Lamotrigine