Master of Science / Department of Clinical Sciences / James K. Roush / Hydrocodone and tramadol are opioid analgesics. No studies have been performed to evaluate the clinical efficacy or pharmacokinetics of hydrocodone/acetaminophen and tramadol in a heterogenous population of dogs. The efficacy of tramadol in dogs has been questioned based on previous pharmacokinetic data. The objectives of this study were to evaluate the analgesic effects of hydrocodone/acetaminophen and tramadol measured by a success/failure model and to determine the pharmacokinetic profile of each drug following the second oral drug dose administration. Fifty client-owned dogs presenting for routine tibial plateau leveling osteotomy were randomized to receive either oral hydrocodone/acetaminophen or tramadol in the postoperative period. A blinded investigator using a modified Glasgow Composite Measure Pain Scale scored each animal. Treatment failures were recorded and compared statistically for differences between the two groups. Blood sampling for pharmacokinetic analysis was initiated after the second oral dose. Mean [plus or minus] SE dose of hydrocodone/acetaminophen administered was 0.5 [plus or minus] 0.04 mg/kg and 16.6 [plus or minus] 1.41 mg/kg for hydrocodone and acetaminophen, respectively. Mean [plus or minus] SE dose of tramadol administered was 5.91[plus or minus] 0.61 mg/kg. The terminal half life, maximal serum concentration (Cmax) and time to maximal serum concentration (Tmax) for tramadol were approximately 1.56 hours, 155.6 ng/mL and 3.90 hours, respectively. Plasma concentrations of the active metabolite O-desmethyltramadol (M1) were low. For hydrocodone, the Cmax and Tmax were approximately 7.90 ng/mL and 3.47 hours, respectively. Plasma concentrations of hydromorphone were low after oral hydrocodone administration. Eighteen of 48 (37.5%) dogs required additional rescue analgesic therapy. This included 10 dogs in hydrocodone group and 8 dogs in the tramadol group (p=0.628). In a group of postoperative patients, no difference in pain scoring could be detected in hydrocodone/acetaminophen and tramadol groups. The pharmacokinetics of tramadol and metabolites were similar to previous studies. Wide variations existed in tramadol drug concentrations and the effects of tramadol are likely independent of the μ-opioid receptor. There is poor metabolism of hydrocodone to hydromorphone in dogs, however, efficacy may be achieved through hydrocodone. The analgesic efficacy of tramadol, 5-7 mg/kg PO q 8 h, and hydrocodone, 0.5 mg/kg PO q 8 h, should be assessed further prior to widespread use in canine postoperative patients.

No description available.

No description available.

The Medical Examiner of Virginia (ME) dataset and the Virginia Department of Forensic Science Driving Under the Influence of Drugs (DUI) datasets were used to determine whether people have the potential to develop tolerances to diphenhydramine, cocaine, oxycodone, hydrocodone, methadone, and morphine. These datasets included the years 2000-2004 and were used to compare the concentrations of these six drugs between people who died from a drug-related cause of death (of the drug of interest) and people who were pulled over for driving under the influence. Three drug pattern groups were created to divide each of the six drug-specific datasets in order to compare concentrations between individuals with the drug alone, the drug and ethanol, or a poly pharmacy of drugs (multiple drugs). An ANOVA model was used to determine if there was an interaction effect between the source dataset (ME or DUI) and the drug pattern groups. For diphenhydramine and cocaine, an interaction was statistically significant, but for the other drugs, it was not significant. The other four drug-specific datasets showed that the DUI and ME were statistically significantly different from each other, and all of those datasets except for methadone showed that there was a statistically significant difference between at least two drug pattern groups. Showing that all of these datasets showed differences between the ME and DUI datasets did not provide sufficient evidence to suggest the development of tolerances to each of the six drugs. One exception was with methadone because there were 14 individuals that had what is defined as a "clinical 'lethal' blood concentration". These individuals provide some evidence for the possibility of developing tolerances.The main outcomes of this study include suggesting changes to make to the ME datasets and the DUI datasets with regard to the way data is kept and collected. Several problems with the fields of these datasets arose before beginning the analysis and had to be corrected. Some of the changes suggested are currently being considered at the Virginia Office of the Chief Medical Examiner as they are beginning to restructure their database.