Influence of food on the oral bioavailability of deramciclane from film-coated tablet in healthy male volunteers

Selectivity in analytical chemistry: Two interpretations for univariate methods

“…This work appears to be the first one to carry out such analysis. It is based among others on our experience with selectivity problems of ion selective electrodes [10][11][12][13], numerous method validations following guidelines for Good Laboratory Practice (GLP) [14,15] and investigations about the selectivity of molecularly imprinted polymers [16,17]. An impulse to this work has been given by important recent recognitions about the selectivity of ion selective electrodes [18][19][20][21] supported by a large body of experimental data.…”

Effects of Food on Drug Absorption

“…On the other hand, adsorption of drugs onto dietary constituents (Toothaker and Welling, 1980;Huupponen et al ., 1984;Welling, 1996;Marathe et al ., 1998;Fleisher et al ., 1999), reduced contact time with GIT, formation of diffusion barrier owing to higher viscosity in the upper small intestine (Fleisher et al ., 1999), higher degradation by gastric acid (Lentz, 2008), complex formation and/or precipitation of the drug by bile salts, heavy metal ions, and/or calcium (Neuvonen, 1976;Welling, 1977;Deppermann and Lode, 1993;Drabant et al ., 2004) could decrease their absorption. The other factors that alter drug absorption are hyper-or hypotonicity (Borowitz et al ., 1971;Ochsenfahrt and Winne, 1971;Welling, 1977), formulation (Karim et al ., 1985a,b;Waldman and Morganroth, 1995;Zhi et al ., 1995;Benziger et al ., 1996;Schug et al ., 2002), contact angle or wetting (Horter and Dressman, 2001), and modification of pH of the urine (Drabant et al ., 2004). The important physicochemical and physiological differences in fasted state and fed state GIT are summarized in Table 14.3.…”

“…The increased GI motility along with increased concentration of bile and lipid digestion products in the fed state is believed to improve dissolution and solubilization of poorly aqueous soluble drugs in the lumen (Rolan et al ., 1994;Humberstone et al ., 1996;Drabant et al ., 2004). In the fasted state, very little intestinal contractions occur, and the luminal contents are essentially stagnant (Horter and Dressman, 2001).…”

“…The presence of food causes longer gastric retention and prolonged gastric acid exposure of acid-labile drugs (e.g., ampicillin, didanosine, erythromycin, isoniazid, and acetylsalicylic acid) in the stomach, resulting in higher degradation (Welling, 1996;Schmidt and Dalhoff, 2002). The presence of food may cause degradation of drugs in the lumen by higher enzyme secretion (Welling, 1996;Drabant et al ., 2004). Alendronic acid, ciprofloxacin, clodronate Na, didanosine, estramustine, etidronic acid, penicillamine, tetracycline, and other fluoroquinolones are known to bind to heavy metals and Ca 2+ to form insoluble chelates (Holmes et al ., 1985;Monk and Campoli-Richards, 1987;Gunnarsson et al ., 1990).…”

Synthesis of deramciclane* labeled with tritium in various positions

“…11,12 Two tritium labelled forms of deramciclane were required with the label in the camphor skeleton, ( [3-3 H]deramciclane (3)) and the side chain ([2-dimethylamino- [2][3] H]ethoxy]deramciclane (9)) for in vitro and in vivo studies to further investigate various aspects of the metabolism and pharmacokinetics of deramciclane. [11][12][13][14][15][16][17][18][19] Previous studies with 3 H and 14 C labelled deramciclane had showed that the metabolism of the camphor skeleton and side chain could be differentiated by virtue of their significantly different biological half-life values.…”