Showing papers by "Julio Benítez published in 2004"

Potential role of cerebral cytochrome P450 in clinical pharmacokinetics: modulation by endogenous compounds.

Abstract: Cytochrome P450 (CYP) enzymes catalyse phase I metabolic reactions of psychotropic drugs. The main isoenzymes responsible for this biotransformation are CYP1A2, CYP2D6, CYP3A and those of the subfamily CYP2C. Although these enzymes are present in the human brain, their specific role in this tissue remains unclear. However, because CYP enzymatic activities have been reported in the human brain and because brain microsomes have been shown to metabolise the same probe substrates used to assess specific hepatic CYP activities and substrates of known hepatic CYPs, local drug metabolism is believed to be likely. There are also indications that CYP2D6 is involved in the metabolism of endogenous substrates in the brain. This, along with the fact that several neurotransmitters modulate CYP enzyme activities in human liver microsomes, indicates that CYP enzymes present in brain could be under various regulatory mechanisms and that those mechanisms could influence drug pharmacokinetics and, hence, drug response. In this paper we review the presence of CYP1A2, CYP2C9, CYP2D6 and CYP3A in brain, as well as the possible existence of local brain metabolism, and discuss the putative implications of endogenous modulation of these isoenzymes by neurotransmitters.

Using a Computerized Drug Prescription Screening System to Trace Drug Interactions in an Outpatient Setting

Abstract: BACKGROUND:Drug—drug interactions are one of the main causes of adverse effects. These events have been studied most often in hospital settings; however, investigations on prescribing based on community practice have shown a high prevalence rate of potential drug interactions.OBJECTIVE:To develop a computerized system able to trace drug interactions quickly through the identification of clinicians issuing potentially unsafe prescriptions.METHODS:We retrospectively evaluated hazardous concomitant prescriptions of hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) and azole antifungals, which were invoiced through 9 months of 2001 within an outpatient setting. The study was conducted in Badajoz, a southern Spanish province, and was divided in three 3–month periods according to the release of 2 warning notes on this drug combination by the Spanish Drug Agency. Prescriptions written during this period were optically scanned each month, and the resulting information, including data from patients, ...

Early detection of drug interactions utilizing a computerized drug prescription handling system—focus on cerivastatin–gemfibrozil

Abstract: Based on the recent cerivastatin experience, we retrospectively evaluated the effect of notifying a drug alert utilizing a computerized drug-handling system. The evaluation was carried out during three periods: period I corresponded to all prescriptions issued during April, 2001 (“baseline period”), before the Spanish Drug Agency issued alerts on the concomitant therapy with cerivastatin and gemfibrozil; period II (June) corresponded to a time in which a first informative note had been released; and period III (July) after the second warning alert was issued. Data collected included the reading of 2,693,656 drug prescriptions, 1,937,083 (71.9%) of which contained patient information. Forty-four patients received combined therapy with cerivastatin and gemfibrozil over the three periods, yielding 55 exposures: 27 during the baseline period, and 28 between periods II and III, when the alert bulletins had already been released. Moreover, 41.6% of doctors included in the follow-up repeated the hazardous prescription during those two periods. The effect of the informative notes about the risk of prescribing cerivastatin and gemfibrozil concomitantly on doctors’ prescribing habits was limited. The system for screening information from drug prescriptions presented herein allows the early detection of drug interactions by identifying the doctors who issue hazardous prescriptions as well as patients at the highest risk of adverse drug reactions, thus allowing a personal feedback with both of them.