[The BIFAP project: database for pharmaco-epidemiological research in primary care]. / El Proyecto BIFAP: Base de datos para la Investigación Farmacoepidemiológica en Atención Primaria.

OBJECTIVES: To create a data base (BIFAP) with information provided by primary care doctors from the National Health System who use a computer at work, to evaluate its validity as a source of pharmaco-epidemiological information and to use it for the study of the efficacy and safety of medicines. JUSTIFICATION: Some data bases, such as the British GPRD, have shown great efficiency in pharmaco-epidemiological research and in analysis of alarm signals in pharmacovigilance: primary care doctors are in a very good position to obtain clinical information from their patients. It is recommended that the impact of medicines on various populations is evaluated, including of course those medicines most used in Spain. PILOT PHASE: January 2000-end of 2003. 300-500 doctors took part: a) monitoring of certain recommendations on recording; b) dispatch every 2 or 3 months to the Spanish Medicines Agency (AEM) of anonymous information with its origin encrypted (basic demographic details, morbidity, prescriptions, other data of epidemiological relevance), which are analysed by computer to check whether they meet adequate recording standards; c) despatch to the AEM of copies of anonymous clinical reports from small samples of patients (for BIFAP validation studies). FEASIBILITY AND PERSPECTIVES: If BIFAP were viable, a standardised procedure for its use and protocols to support it as a research tool would be put in place.

[Factors that determine intensity of response to treatment with tiludronate in Paget's disease]. / Factores que determinan la intensidad de la respuesta al tratamiento con tiludronato en la enfermedad de Paget.

OBJECTIVE: To investigate the influence of both clinical and pharmacokinetic factors as determinants of response to tiludronate in Paget's bone disease (PBD). PATIENTS AND METHODS: Twenty six PBD patients with serum alkaline phosphatase (SAP) levels at least twice the normal upper limit were enrolled. The sample included 17 (65%) men and 9 (35%) women whose mean age (SD) was 60.3 (9.8) (range: 38-76). Each patient received 400 mg/day of tiludronate, per os, for 90 (6) days. The SAP variations were considered as the main parameter of response. Plasma concentrations of tiludronate were assayed using the HPLC method with UV detection; the maximum and minimum (Cmin) concentration, as well as the area under a concentration-time curve were calculated. Multivariate regression analysis was performed to assess the influence on tiludronate effect. RESULTS: Mean (SD) percent reduction of SAP from the initial values ranged from 30.5 (13.9) at the end of the first month of drug intake to a nadir of 76.1 (8.8) achieved 6 months after the treatment was stopped. Serum SAP activity fell to normal range in 7 (27%) patients at the end of the therapy period, in 17 (65%) three months later, and in 18 (69%) one year thereafter. One year after the treatment ended only one patient had evidence of relapse. Final multivariate regression model showed that the percent reduction of SAP increases by 11.9 percent points per Cmin tiludronate unit and by 0.006 points per basal SAP unit, and decreases by 0.52 per year of age. Out of 13 patients with bone pain, 9 (69%) experienced relief within the second and third months of treatment. No clinical or laboratory severe side effects were seen and only five patients (19%) had mild adverse events. CONCLUSIONS: These results confirm that tiludronate leads to a marked suppression of PDB clinical and biochemical activity. Cmin of tiludronate in plasma is the best predictor of biochemical response.