In vivo biopharmaceutical characterisation of a new formulation containing the antiepileptic drug lamotrigine in comparison to plain and dispersible/chewable lamotrigine tablets.

AIM: Two studies in healthy male volunteers were carried out to evaluate the pharmacokinetic profile of a new divisible formulation of lamotrigine (CAS 84057-84-1, Plexxo, Lamotrigin Desitin) in plasma in comparison to plain or dispersible lamotrigine tablets. METHODS: The plasma pharmacokinetics of lamotrigine were analysed after administration of single doses of 100 mg lamotrigine given as one tablet of the new formulation and either the plain or the dispersible reference formulation in two separate studies. In each study the data of 24 subjects were analysed according to the study protocol. Venous blood samples were taken at appropriate intervals up to 120 h after dosing. Concentrations of lamotrigine were determined in plasma by a validated HPLC method using UV detection. RESULTS AND CONCLUSION: In both studies, mean plasma concentration-time profiles of the new lamotrigine formulation and both reference formulations ran nearly in parallel. The pharmacokinetic mean data calculated from different subject groups of the two studies were very similar. The mean ratios of the main pharmacokinetic parameters and the corresponding 90% confidence intervals of AUC(0-t), AUC(0-inf) and C(max) were 103% (99.7-105.7), 103% (99.6-107.3) and 101% (95.2-106.6) for the comparison with the plain lamotrigine tablet and 100% (98.0-102.8), 100% (96.5-102.8) and 102% (99.1-105.3) for the comparison with the dispersible/chewable tablet, respectively. The most frequently reported adverse events possibly related to the administration of lamotrigine were headache and dizziness in both studies. It is concluded that the new divisible lamotrigine formulation is bioequivalent with regard to rate and extent of absorption to both the plain reference lamotrigine product and to the dispersible/chewable reference product.

Single dose pharmacokinetics of alpha-dihydroergocryptine in patients with moderate to severe renal insufficiency.

AIM: This study was carried out to evaluate the pharmacokinetic profile of alpha-dihydroergocryptine (CAS 14271-05-7, DHEC, Almirid) in plasma and urine in patients with moderately to severely impaired renal function (creatinine clearance < 30 ml.min-1.1.73 m-2), following administration of single oral doses. METHODS: This was an open, nonrandomized trial. Seven patients with chronic renal disease and six healthy subjects received a single dose of 20 mg DHEC. Blood and urine samples were taken at specified intervals up to 72 h after dosing. Concentrations of unchanged DHEC were determined by radio-immunoassay (RIA) and concentrations of unchanged DHEC plus pooled metabolites by enzyme-immunoassay (EIA), respectively. RESULTS: In patients with impaired renal function, the mean Cmax and AUC(0-infinity) values for unchanged DHEC were 2.1 (95% confidence interval CI: 0.99 to 4.42) and 1.85 (95% CI: 0.72 to 4.77) times larger than in controls. The 24-h urinary excretion was only 0.3 (95% CI: 0.12 to 0.71) times that in healthy subjects. Similar findings were recorded for total DHEC plus metabolites. CONCLUSIONS: As treatment with DHEC is in general uptitrated starting with doses as low as 5 mg DHEC, which are then increased while accounting for individual effects both in terms of efficacy and tolerability, the observed range of effects of impaired renal function on DHEC's pharmacokinetics does not suggest the need to revise this policy, although lower end-doses are likely to be achieved.