Overall objectives of this proposed research are to delineate pharmacokinetic parameters from the time course of absorption, distribution, metabolism and excretion of certain selected drugs that are implicated in abuse, using the dog as the basic animal model. These pharmacokinetic studies after intravenous and oral administration of various drugs to be studied will include morphine, codeine, buprenorphine, heroin and selected narcotic antagonists, phencyclidine, cocaine and methadone. Analytical methodology will be continued to be developed so that these drugs and their available metabolites can be monitored in available biological fluids such as blood, urine and bile at the necessary levels to establish precise pharmacokinetic models. Our prior studies have produced methods applicable to the assay of such drugs and their metabolites at the picogram level which is the necessary sensitivity to perform such studies. These developed analytical methods of high sensitivity are needed in forensic medicine. The protein binding and erythrocyte partition of these compounds will be determined. The physicochemical parameters and rate-pH profiles of these compounds, their interconversions and degradations will be evaluated. Such studies are vital to understand and map in vivo transformations. Long term goals are to develop procedures and models to serve as the basis for the eventual evaluation of the pharmacokinetics of these compounds in humans, to correlate psychic and pharmacodynamic effects with the time courses of the drugs and thier metabolites and to define the mode of action of antagonists.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Research Project (R01)
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Pharmacology I Research Subcommittee (DABR)
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University of Florida
Schools of Pharmacy
United States
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Hughes, John R; Pillitteri, Janine L; Callas, Peter W et al. (2004) Misuse of and dependence on over-the-counter nicotine gum in a volunteer sample. Nicotine Tob Res 6:79-84
Garrett, E R; Seyda, K; Marroum, P (1991) High performance liquid chromatographic assays of the illicit designer drug ""Ecstasy"", a modified amphetamine, with applications to stability, partitioning and plasma protein binding. Acta Pharm Nord 3:9-14
Garrett, E R; Chandran, V R (1990) Pharmacokinetics of morphine and its surrogates. X: Analyses and pharmacokinetics of buprenorphine in dogs. Biopharm Drug Dispos 11:311-50
Langguth, P; Khan, P J; Garrett, E R (1990) Pharmacokinetics of morphine and its surrogates. XI: Effect of simultaneously administered naltrexone and morphine on the pharmacokinetics and pharmacodynamics of each in the dog. Biopharm Drug Dispos 11:419-44
Garrett, E R; Chandran, V R (1989) Pharmacokinetics of morphine and its surrogates. IX: Discrepancies among infused buprenorphine plasma concentrations sampled from different veins. J Pharm Sci 78:644-7
Garrett, E R; Shyu, W C; Ulubelen, A (1986) Pharmacokinetics of morphine and its surrogates. VIII: Naloxone and naloxone conjugate pharmacokinetics in dogs as a function of dose and as affected by simultaneously administered morphine. J Pharm Sci 75:1127-36
Garrett, E R; Derendorf, H; Mattha, A G (1985) Pharmacokinetics of morphine and its surrogates. VII: High-performance liquid chromatographic analyses and pharmacokinetics of methadone and its derived metabolites in dogs. J Pharm Sci 74:1203-14
Garrett, E R; el-Koussi A el-D (1985) Pharmacokinetics of morphine and its surrogates V: Naltrexone and naltrexone conjugate pharmacokinetics in the dog as a function of dose. J Pharm Sci 74:50-6
Garrett, E R; Chandran, V R (1985) Pharmacokinetics of morphine and its surrogates VI: Bioanalysis, solvolysis kinetics, solubility, pK'a values, and protein binding of buprenorphine. J Pharm Sci 74:515-24