Bioequivalency and dose proportionality of three tableted promethazine products

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Abstract
Data from a five‐way crossover study in human subjects using four talented promethazine products and a promethazine solution are presented. All products were administered as a single oral dose. The five objectives of the study were to investigate bioequivalency, to estimate dose proportionality at two dose levels, to establish validity of a reference production solution for future bioequivalency studies, to estimate intersubject variation, and to compare bioavailability/tablet dissolution data. Blood samples were collected at given intervals over a 24‐hour period and analysed for promethazine using an HPLC technique. Pharmacokinetic parameters were calculated using standard procedures and a two‐way analysis of variance (ANOVAR) was used to assess whether the differences were statistically significant. The AUC0→∞ data from the ANOVAR analysis showed that the 50 mg innovator and generic products and the 50 mg solution were not significantly different. However, the innovator product had a significantly lower Cmax and longer tmax than the solution. The generic product did not differ significantly from the solution. Promethazine was found to exhibit linear dose proportionality in the range and product studied. Intersubject variation was high for all parameters (23 to 63 per cent) and the in vivo and in vitro data showed a positive relationship.