To investigate the so-called "drift" with generic-generic drug substitution, a single-dose, four-way crossover comparative bioavailability study was performed involving 24 healthy subjects and three generic and one branded formulation of a tablet containing 800 mg gabapentin as test medication. The results showed that the 90% confidence intervals (CIs) for the area under the drug concentration-time curve (AUC(0-t)) and for the peak drug concentration (C(max)) were within the acceptance range of 80-125% for all comparisons. The safety profiles of the different gabapentin formulations were comparable. To conclude, all three generic formulations of gabapentin were found to be bioequivalent with the branded formulation and with each other, indicating that the formulations are interchangeable. These results strongly indicate the absence of "drift" with gabapentin generic-generic substitution.

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PurposeTo date, the interchangeability of generic drugs has only been investigated for a limited number of medicines. The objective of this study was to investigate generic-generic drug interchangeability in a large subset of generic formulations in order to cover a broad spectrum of drugs.MethodsOrally administered drugs for investigation in this study were selected using strict, predefined criteria, with the purpose to avoid bias. This selection procedure yielded atorvastatin, bicalutamide, naratriptan, olanzapine, perindopril, and venlafaxine. Further, ciclosporin, tacrolimus, and mycophenolate mofetil were investigated as test immunosuppressants. Adjusted indirect comparisons were conducted between generic drugs containing the same active substance, and the 90 % confidence interval (CI) for AUC and Cmax was calculated.ResultsIn total, 120 bioequivalence studies were identified in the Dutch medicine regulatory agency’s database, allowing 292 indirect comparisons between generic drugs. The indirect comparison results indicated that in the vast majority of cases, i.e., 80.5 %, the 90 % CIs for both AUCt and Cmax fell within the bioequivalence criteria (in 90.1 and 87.0 % for AUCt and Cmax, respectively). In 1 % of the 292 indirect comparison for AUCt and 3 % for Cmax, a wider range of 75–133 % (or 80–125 %) was exceeded.ConclusionsOverall, our study suggests that exposure-related risks associated with the exchange of different generic drugs in clinical practice are not increased to a relevant extent compared to the situation in which a generic is exchanged with the innovator.Electronic supplementary materialThe online version of this article (doi:10.1007/s00228-015-1878-z) contains supplementary material, which is available to authorized users.

Catalytic combustion is an efficient method to eliminate CO and volatile organic compound (VOC) pollutants. CuMn2O4 spinel is a high-performance non-noble metal oxide catalyst for catalytic combustion and has the potential to replace noble metal catalysts. In order to further improve the catalytic activity of CuMn2O4 spinel, we propose a simple and low-cost approach to introduce numerous oxygen and metal vacancies simultaneously in situ on the CuMn2O4 spinel surface for the catalytic combustion of CO and VOCs. Alkali treatment was used to generate oxygen vacancies (VO), copper vacancies (VCu), and novel active sites (VO combines with Mn2O3 at the interface between Mn2O3(222) and CuMn2O4(311)) on the CuMn2O4 spinel surface. In the catalytic combustion of CO and VOCs, the vacancies and new active sites showed high activity and stability. The oxidation rate of CO increased by 4.13 times at 160 °C, and that of toluene increased by 11.63 times at 250 °C. Oxygen is easier to adsorb and dissociate on VO and novel sites, and the dissociated oxygen also more easily participates in the oxidation reaction. Furthermore, the lattice oxygen at VCu more readily participates in the oxidation reaction. This strategy is beneficial for the development of defect engineering on spinel surfaces and provides a new idea for improving the catalytic combustion activity of CuMn2O4 spinel.