Aims 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 l −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 dosage5concentration 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 l −1 ) was widely accepted and increasingly applied in clinical practice in the management of patients with epilepsy.

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Summary:Purpose: Lamotrigine (LTG) is recognised as effective add-on therapy for focal epilepsies, but this is the first double-blind, placebo-controlled, crossover study in treatmentresistant generalised epilepsy.Methods: The study consisted of 2 x 8-week treatment periods followed by a 4-week washout period. Patients received doses of either 75 or 150 mg daily, depending on their concomitant antiepileptic drugs (AEDs). Long-term continuation was offered at the end of the study with open-label LTG.Results: Five centres in Australia recruited 26 patients who were having absence, myoclonic, or generalized tonic-clonic seizures or a combination of these. Twenty-tv?o patients completed the study. There was a significant reduction in frequency of both tonic-clonic and absence seizure types with LTG. A 250% decrease in seizures was observed for tonic-clonic seizures in 50% of cases and for absence seizures in 33% of evaluable cases. Rash was the only adverse effect causing discontinuation. Twenty-three of 26 opted for open-label LTG, with 20 still receiving LTG for a mean of 26 months. In these 20, 80% had 250% seizure reduction and five (25%) were seizure free.Conclusions: This study shows that LTG is effective add-on therapy in patients with refractory generalised epilepsies. Statistically significant reduction in seizures in both absence and tonic-clonic seizure types was seen even with low doses of LTG.

The Western and Thick-billed Grasswrens (Aves: Passeriformes: Maluridae:Amytornis textilis and A. modestus, respectively) exemplify issues surrounding the evolution, biogeography and conservation of Australia's arid and semi-arid zone fauna. The two species together have historically occurred across much of southern Australia. They showed high intraspecific taxonomic diversity and short range endemism but suffered high rates of recent anthropogenic extinction. Of 11 named and one un-named subspecies, five are extinct and three are vulnerable or critically endangered. To clarify taxonomic issues, and to understand their pre-extinction phylogeography and identify extant populations and taxa of conservation value, we sequenced ~1000 bp of the mtDNA ND2 gene from all extant populations and all but one extinct population. We confirmed reciprocal monophyly of A. modestus and A.

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