Clinical safety of flurbiprofen.

Data from 58 premarketing studies of the nonsteroidal antiinflammatory drug flurbiprofen were pooled for analyses of adverse drug reactions (ADRs). These studies included 5602 patients treated with flurbiprofen (N = 4123), aspirin (N = 1033), or placebo (N = 446) for varying durations. Diagnoses included rheumatoid arthritis, osteoarthritis, and other painful musculoskeletal conditions. In these studies serious upper gastrointestinal ADRs occurred in flurbiprofen-treated patients at less than one half the rate seen in aspirin-treated patients. The incidence of serious urinary tract ADRs was lower with flurbiprofen than with aspirin. The flurbiprofen group had no serious clinical ADRs related to the hemic/lymphatic system. The most common laboratory abnormality was a decrease in hematocrit, which occurred less often than in the aspirin group. We also evaluated serious flurbiprofen-related ADRs in 4370 patients in a variety of other studies and reviewed published reports of flurbiprofen clinical trials and case reports. These reviews showed no additional, unanticipated patterns of intolerance. These clinical safety data indicate that in the doses studied, flurbiprofen is a well tolerated agent for patients requiring nonsteroidal antiinflammatory drug therapy.

Altering the progression of human alveolar bone loss with the non-steroidal anti-inflammatory drug flurbiprofen.

The treatment of human periodontal diseases relies on mechanical and antimicrobial suppression of the etiologic bacteria. The ability to alter the progression of periodontitis by additionally blocking host pathways involved in the destructive process is an area of current research. Prostaglandins and other metabolites of arachidonic acid are believed to be important host mediators of the bone resorption of diseases such as periodontitis. We have previously examined the effect of inhibitors of prostaglandin production, non-steroidal anti-inflammatory drugs (NSAIDs), on inhibiting alveolar bone loss in beagles. The present study was designed to examine the effect of the NSAID, flurbiprofen, on slowing the radiographic loss of alveolar bone in the human. Fifty-six individuals with radiographic evidence of alveolar bone loss were recruited for study. Forty-four patients remained in the study for the data analysis of loss of alveolar bone. Following a 6 month baseline pretreatment period to measure the radiographic progression of bone loss, half of the patients were administered flurbiprofen, 50 mg. b.i.d., while half were administered a placebo. All patients received a subgingival scaling and pumice by a hygienist every 6 months. The rate of alveolar bone loss in a 2 year treatment period was compared to the baseline 6 month pretreatment period within and between patient groups. Throughout the study, teeth exhibiting obvious loss of bone were exited from study and treated with conventional mechanical therapy. At the end of the pretreatment period both patient groups had a similar mean rate of alveolar bone loss.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacologic characterization of nicotine-induced conditioned place preference.

Rats received subcutaneous injections of either nicotine (0.1 to 1.2 mg/kg) or saline (1.0 ml/kg) immediately prior to conditioning sessions in a conditioned place preference (CPP) paradigm. The drug was paired for 3 conditioning sessions with the non-preferred environment of a 3 compartment place preference apparatus; saline was paired with the preferred environment. The animals were then tested for place preference by determining the proportion of time spent in the preferred and non-preferred compartments during a 15 min test session. Using a statistical method developed for the CPP paradigm, dose-response curves were obtained for the rewarding and aversive effects of nicotine as measured by its ability to alter previously determined baseline preferences obtained from the control animals. Nicotine's rewarding and aversive effects were linearly correlated with respect to dosage within the range of 0.1-0.8 mg/kg (reward increased and aversion decreased). A decrease in reward and an increase in aversion was measured at the 1.2 mg/kg treatment level. Mecamylamine hydrochloride and hexamethonium bromide (at 1.0 mg/kg of the base or ion, respectively) were also tested using the CPP paradigm. While neither compound produced place preferences when administered alone, mecamylamine did block the rewarding effects of 0.8 mg/kg of nicotine when administered 30 minutes prior to the nicotine conditioning sessions. Hexamethonium did not alter nicotine-induced reinforcement. The data suggest that nicotine and its rewarding effects as measured by CPP are primarily mediated by central rather than peripheral events.