Comparative pharmacokinetics of submucosal vs. intravenous flumazenil (Romazicon) in an animal model.

PURPOSE: This study was performed to determine the bioavailability and local tissue toxicological safety of flumazenil (Romazicon) when administered by oral submucosal (SM) as opposed to intravenous (i.v.) injection. METHODS: Six dogs each received SM flumazenil (0.2 mg), and their serum was collected at predetermined time intervals (0-2 h) and frozen (-70 degrees C). Seven days later, the dogs received an identical dose of i.v. flumazenil, and serum samples were again collected, as above. Comparative quantitation of flumazenil levels (i.v. vs. SM) was made using a sensitive HPLC assay (UV detection). Direct/local drug toxicity was visually scored by unbiased raters of color photographs (test and control mucosa) taken at 1, 2, and 7 days following SM flumazenil injection. An oral pathologist examined slides processed from control and treatment tissues (hematoxylin and eosin staining) taken (punch biopsy) 1 week following SM injection to compare with direct clinical scores. RESULTS: Serum flumazenil levels reached a plateau (8.5 +/- 1.5 ng/mL, mean +/- SD) within 4 min of SM drug injection and declined thereafter to -2 ng/mL by 2 h. Bioavailability of SM flumazenil was 101 +/- 14%, based upon measuring the area under the serum concentration-time curves over 1.5 h (AUC 0-1.5 h, SM vs. i.v. drug). Thus, serum drug levels following SM drug administration were broadly comparable to those obtained during the elimination phase of corresponding i.v. drug delivery. Regarding drug tissue toxicity, no evidence of direct drug toxicity was observed by unbiased raters of color photographs (test and control mucosa) taken at 1, 2, and 7 days following SM flumazenil injection. Following pathologic review, no difference was seen in the degree of inflammation between treatment and control tissue. CONCLUSION: At the quantity and concentration used, SM drug flumazenil administration appears to be both a safe and a viable alternative to bolus i.v. drug delivery and worthy of further investigation.

Dental odontomas: a retrospective study of 104 cases.

An odontoma refers to any tumor of odontogenic origin. Three distinct types of odontomas have been distinguished in the dental literature: complex, compound, and ameloblastic fibro-odontoma. Odontomas are usually associated with overly retained primary and unerupted permanent teeth. The exact etiology of odontomas is unknown, but local trauma, infection, inheritance, and genetic mutation have been postulated as possible causes of odontomas. Studies have found that males are more likely than females to have odontomas, with most frequent occurrence in the second decade of life. One hundred four biopsy reports with a diagnosis of odontoma were analyzed for age, race, gender, location, pre-operative diagnosis, and postoperative laboratory findings. Most odontomas occurred in the 11-20 age group, with Caucasians predominating. The majority were located in the maxilla, and 85 percent were correctly diagnosed clinically by the attending dentist prior to confirmation by histologic pathology reports of the biopsy specimens. The vast majority were compound odontomas (64.4%) with complex odontomas comprising 31.0% of the total lesions. No ameloblastic fibro-odontomas were diagnosed.