COMBINE Study

The only kinetic data reported are in a Ph.D. thesis (41). Integral order kinetics were usually not obtained for the reaction of a number of ketones with piperidine and a number of secondary amines with cyclohexanone. A few of the combinations studied (cyclopentanone plus piperidine, pyrrolidine, and 4-methylpiperidine, and N-methylpiperazine plus cyclohexanone) gave reactions which were close to first-order in each reactant. Relative rates were based on the time at which a 50% yield of water was evolved. For the cyclohexanone-piperidine system the half-time (txn) for the 3 1 ratio was 124 min and for the 1 3 ratio 121 min. It appears that an... 

Ciraulo DA, Jaffe JH Tricyclic antidepressants in the treatment of depression associated with alcoholism. Clin Psychopharmacol 1 146—150, 1981 Ciraulo DA, Nace E Benzodiazepine treatment of anxiety or insomnia in substance abuse patients. Am J Addict 9 276—284, 2000 Ciraulo DA, Barnhill JG, Jaffe JH, et al Intravenous pharmacokinetics of 2-hydroxy-imipramine in alcoholics and normal controls. J StudAlcohol 51 366-372, 1990 Ciraulo DA, Knapp CM, LoCastro J, et al A benzodiazepine mood effect scale reliability and validity determined for alcohol-dependent subjects and adults with a parental history of alcoholism. Am J Drug Alcohol Abuse 27 339—347, 2001 Collins MA Tetrahydropapaveroline in Parkinson s disease and alcoholism a look back in honor of Merton Sandler. Neurotoxicology 25 117-120, 2004 COMBINE Study Research Group Testing combined pharmacotherapies and behavioral interventions in alcohol dependence rationale and methods. Alcohol Clin Exp Res 27 1107-1122, 2003a... 

The mechanism of the first half-reaction has been studied by a combination of reductive titrations with CO and sodium dithionite and pre-steady-state kinetic studies by rapid freeze quench EPR spectroscopy (FQ-EPR) and stopped-flow kinetics 159). These combined studies have led to the following mechanism. The resting enzyme is assumed to have a metal-bound hydroxide nucleophile. Evidence for this species is based on the similarities between the pH dependence of the EPR spectrum of Cluster C and the for the for CO, deter-... 

A system has been constructed which allows combined studies of reaction kinetics and catalyst surface properties. Key elements of the system are a computer-controlled pilot plant with a plug flow reactor coupled In series to a minireactor which Is connected, via a high vacuum sample transfer system, to a surface analysis Instrument equipped with XFS, AES, SAM, and SIMS. When Interesting kinetic data are observed, the reaction Is stopped and the test sample Is transferred from the mlnlreactor to the surface analysis chamber. Unique features and problem areas of this new approach will be discussed. The power of the system will be Illustrated with a study of surface chemical changes of a Cu0/Zn0/Al203 catalyst during activation and methanol synthesis. Metallic Cu was Identified by XFS as the only Cu surface site during methanol synthesis. 

Pickett et al. 1997) in MORE samples played an important role, not only to address the problem of magma transfer times, but also in the development of dynamic melting models able to sustain such disequilibria over long periods. In subduction zone volcanoes, the combined study of and Ra- °Th disequilibria place unique constraints on the... 

Rainer, D. R., Vesecky, S. M., Koranne, M. et al. (1997) The CO + NO reaction over Pd A combined study using single-crystal, planar-model-supported, and high-surface-area Pd/Al203 catalysts , J. Catal., 167, 234. 

Combination studies of olaparib are being explored clinically with a number of agents, including irinotecan, dacarbazine, carboplatin, gemcitabine, doxorubicin, cisplatin, and topotecan. 

Another distinct property of mixed complexes which we mention here is the possibility to observe two activation regimes of relaxation of magnetization. One of them corresponds to reversal of magnetization of individual ions, at higher temperatures, and the other is related to climbing over the barrier built from the exchange multiplets of the complex. The coexistence of these two relaxation regimes has been recently revealed in the Co Dy ,11 complex in a combined study... 

Fulcher SM Rifaximin Combined Study of Effects on Fertility and Embryo-Fetal Toxicity in CD Rats by Oral Gavage Administration. Eye, Huntington Life Sciences, 2000. 

With the possible exception of combining the female fertility component with the embryo-fetal development component, the combined-study approach is used often. The female fertility and embryo-fetal development components are needed to... 

A large volume of published data provides examples of application of PK/PD. Table 18.3 lists some of the most recent attempts to project PK and PD in combined studies. 

Verkleij, A.J., Zwaal, R.F., Roelofsen, B., Comfurius, P., KasteUjn, D. and van Deenen, L.L.M., 1973, The asymmetric distribution ofphosphoUpids in the human red cell membrane. A combined study using phospholipases and freeze-etch electron microscopy. 

Stein E, Pankiewicz J, Harsch HH, Cho JK, Fuller SA, Hoffmann RG, Hawkins M, Rao S, Bandettini PA, Bloom AS (1998) Nicotine-induced limbic cortical activation in the human brain a functional MRI smdy. Am J Psychiatry 155 1009-1015 Sziraki I, Lipovac MN, Hashim A, Sershen H, Allen D, Cooper T, Czobor P, Lajtha A (2001) Differences in nicotine-induced dopamine release and nicotine pharmacokinetics between Lewis and Fischer 344 rats, Neurochem Res 26 609-617 Terborg C, Birkner T, Schack B, Witte OW (2002) Acute effects of cigarette smoking on cerebral oxygenation and hemodynamics a combined study with near-infrared spectroscopy and transcranial Doppler sonography, J Neurol Sci 205 71-75 Thompson JC, WUby G, Stough C (2002) The effects of transdermal nicotine on inspection time. Hum Psychopharmacol 17 157-161... 

Insight into the Mechanism of Action via Hemagglutination Assay and Drug Combination Studies... 

The combined repeated dose toxicity study with the reproduction/developmental toxicity screening test (OECD TG 422) is, for the repeated dose toxicity part, concordant with the standard 28-day oral toxicity study (OECD TG 407) except for use of pregnant females and longer exposure duration (about 6 weeks for males and approximately 54 days for females) in the combined study compared to the standard 28-day study. 

The immediate impact of this research will be a clearer understanding of ligand motions during photoelimination reactions. In particular, comparative studies of molecular motions in the gas phase (using ultrafast electron diffraction) and in the liquid phase should become a source of very detailed understanding of the influence of solvation on chemical processes. Such combined studies in collaboration with Peter Weber, Dept, of Chemistry, Brown University are planned. 

---