Clinical study of lamotrigine and valproic acid in patients with epilepsy: using a drug interaction to advantage?

Lamotrigine (LTG) is one of the newer antiepileptic drugs which has been shown to have a spectrum of drug interactions (including with other epilepsy drugs) that can have a pronounced effect on LTG kinetics. The present study examined the LTG metabolic inhibition dose-response relationship with valproic acid (VPA) in eight patients with epilepsy with a view to using this to benefit the patient. This could benefit the patient not only by attaining higher plasma LTG concentrations with "standard" dosages of LTG, but also possibly by achieving better seizure control through providing a less variable peak-to-trough fluctuation in LTG concentrations as a result of extending the half-life of LTG. The dosages of VPA trialed were 0, 200, 500, and 1,000 mg/d which resulted in a mean increase in LTG area under the curve of 83.7 +/- 14.7% at 200 mg VPA/d, to and 160 +/- 37.9% at 1,000 mg VPA/d. The presence of concomitant enzyme inducers in some patients did not influence the percentage increase from baseline in half-life observed, although clearly those on inducers started from a lower absolute half-life as a result of the induction. The effect was shown to be quite variable, particularly at the highest dosage of VPA tested (1,000 mg/d), suggesting that this effect could be best applied with the support of the therapeutic drug monitoring laboratory determining plasma LTG concentrations to allow individualization of the LTG dosage.

Evaluation of the tacrolimus II microparticle enzyme immunoassay (MEIA II) in liver and renal transplant recipients.

We evaluated the MEIA II with blood samples with added tacrolimus (3.0, 5.0, 11.0, and 22.0 microg/L). The assay had acceptable recoveries (99-103%) and intraday imprecision (<16.0%) across the range of concentrations studied, except for the recoveries at 3.0 microg/L (86.3%) and 5.0 microg/L (80.7%). Comparison of liver (n = 116) and renal (n = 113) patient samples measured by MEIA II against HPLC-tandem mass spectrometry (HPLC-MS/MS) found a mean overestimation of 15.6%. From these comparison data it can be calculated that at values of 5 and 20 microLg/L in liver or renal transplant patient samples, measured by HPLC-MS/MS, MEIA II will have the corresponding range estimates of 3.6-7.9 microg/L and 20.9-25.4 microg/L, respectively. No clinically significant difference in results, in terms of overestimation or correlation, was observed between the two transplant groups studied. The MEIA II is an improvement on the previous MEIA I and is suitable for the therapeutic drug monitoring of tacrolimus where HPLC-MS/MS is unavailable.