Average bioequivalence of single 500 mg doses of two oral formulations of levofloxacin: a randomized, open-label, two-period crossover study in healthy adult Brazilian volunteers

Average bioequivalence of two 500 mg levofloxacin formulations available in Brazil, Tavanic(c) (Sanofi-Aventis Farmacêutica Ltda, Brazil, reference product) and Levaquin(c) (Janssen-Cilag Farmacêutica Ltda, Brazil, test product) was evaluated by means of a randomized, open-label, 2-way crossover study performed in 26 healthy Brazilian volunteers under fasting conditions. A single dose of 500 mg levofloxacin tablets was orally administered, and blood samples were collected over a period of 48 hours. Levofloxacin plasmatic concentrations were determined using a validated HPLC method. Pharmacokinetic parameters Cmax, Tmax, Kel, T1/2el, AUC0-t and AUC0-inf were calculated using noncompartmental analysis. Bioequivalence was determined by calculating 90% confidence intervals (90% CI) for the ratio of Cmax, AUC0-t and AUC0-inf values for test and reference products, using logarithmic transformed data. Tolerability was assessed by monitoring vital signs and laboratory analysis results, by subject interviews and by spontaneous report of adverse events. 90% CIs for Cmax, AUC0-t and AUC0-inf were 92.1% - 108.2%, 90.7% - 98.0%, and 94.8% - 100.0%, respectively. Observed adverse events were nausea and headache. It was concluded that Tavanic(c) and Levaquin(c) are bioequivalent, since 90% CIs are within the 80% - 125% interval proposed by regulatory agencies.

Assessing subjective memory complaints: a comparison of spontaneous reports and structured questionnaire methods

ABSTRACTBackground:Subjective memory complaints (SMCs) are a common occurrence for adults, which increase with age, and cause considerable distress. Traditionally SMCs have been assessed by either questionnaires, which ask whether a person has experienced given examples of SMCs, or open-ended questions which elicit spontaneous reports of SMCs. However, little is known about how these methods of assessment might influence reporting of SMCs.Methods:Four hundred and twenty one adults aged 40 years and above were surveyed about SMCs using spontaneous report and questionnaire methods.Results:As expected, spontaneously reported SMCs were fewer in number and rated more distressing overall than SMCs endorsed on a questionnaire. However, comparison of individual SMCs revealed that distress ratings tended to be higher when assessed in a questionnaire than spontaneously reported, which may be due to the context of a questionnaire causing inflated ratings. Participants also reported SMCs which were not well assessed by the questionnaire, including some which were among the most distressing SMCs overall. Conversely, other SMCs were over-sampled by the questionnaire and did not feature in spontaneous reports.Conclusions:Implications for clinical assessment of SMCs are that open-ended questioning might be preferable to initial use of prescriptive questionnaires, in order to elicit SMCs that are most distressing. While use of questionnaires may reveal endorsement of a wider range of SMCs than are spontaneously reported, they can take focus away from, or even fail to assess, those SMCs which cause most subjective distress (and therefore should be the target of interventions).

Disproportionality methods for pharmacovigilance in longitudinal observational databases

Data mining disproportionality methods (PRR, ROR, EBGM, IC, etc.) are commonly used to identify drug safety signals in spontaneous report system (SRS) databases. Newer data sources such as longitudinal observational databases (LOD) provide time-stamped patient-level information and overcome some of the SRS limitations such as an absence of the denominator, total number of patients who consume a drug, and limited temporal information. Application of the disproportionality methods to LODs has not been widely explored. The scale of the LOD data provides an interesting computational challenge. Larger health claims databases contain information on more than 50 million patients and each patient has records for up to 10 years. In this article we systematically explore the application of commonly used disproportionality methods to simulated and real LOD data.