caa a22 4500 477058019 CHVBK 20180405111352.0 cr unu---uuuuu 170330e19960101xx s 000 0 eng 10.1007/BF00226328 doi (NATIONALLICENCE)springer-10.1007/BF00226328 Design of a suitable formulation of FK613, a novel antiallergic agent, based on its pharmacokinetic and pharmacodynamic properties in healthy subjects [Elektronische Daten] [T. Uematsu, S. Nagashima, H. Inaba, M. Nakashima, T. Kajiho, H. Kageyama, A. Sugiyama] The pharmacokinetic and pharmacodynamic properties of FK613, a novel indolyl piperidine derivative, were investigated after oral administrations of 5, 10 and 20 mg in hard gelatin capsules to healthy male volunteers. FK613 was rapidly and almost completely absorbed, and >89% was recovered in the urine as the unchanged form. The urinary excretion of FK613 was linearly correlated with plasma concentration and its low water solubility was the main concern regarding the safety. In another experiment using a double-blind crossover design, in which 0 (placebo), 5 and 20 mg FK613 were administered to determine the plasma concentration-effect relationship, suppression of the intradermal histamine-induced skin reaction by FK613 was observed. Thus, the maintenance of a plasma concentration of FK613 in the range of 80-250 ng · ml-1 was recommended to ensure the suppression of histamine-induced wheal by >50% and not to exceed the solubility in urine. To achieve this, a new hydrogel-type formulation of FK613 was developed, with the aim both of delaying its absorption, so as to suppress the sharp rise in plasma concentration, and of maintaining the effective concentration for a longer period of time. This formulation was administered after meals at the doses of 20, 30, 40, 50 and 60 mg, and at repeated doses of 40 mg twice daily for 6.5 days to evaluate the pharmacokinetics and safety in healthy subjects. The area under the plasma concentration curve increased linearly with dose, whereas maximum plasma concentration (Cmax) tended to peak as dose increased, indicating the desirable properties of this formulation. Although Cmax exceeded 250 ng/ml at doses of 30 mg or more, no urinary crystal formation was observed on careful inspection of urine. Springer-Verlag, 1996 Antiallergic drug nationallicence FK613 nationallicence pharmacokinetics nationallicence histamine skin-test nationallicence drug formulation nationallicence urinary excretion nationallicence safety nationallicence Uematsu T. Department of Pharmacology, Hamamatsu University School of Medicine, 431-31, Hamamatsu, Japan aut Nagashima S. Department of Pharmacology, Hamamatsu University School of Medicine, 431-31, Hamamatsu, Japan aut Inaba H. Department of Pharmacology, Hamamatsu University School of Medicine, 431-31, Hamamatsu, Japan aut Nakashima M. Department of Pharmacology, Hamamatsu University School of Medicine, 431-31, Hamamatsu, Japan aut Kajiho T. Department of Clinical Pharmacology, Fujisawa Pharmaceutical Co. Ltd., 532, Osaka, Japan aut Kageyama H. Department of Clinical Pharmacology, Fujisawa Pharmaceutical Co. Ltd., 532, Osaka, Japan aut Sugiyama A. Department of Clinical Pharmacology, Fujisawa Pharmaceutical Co. Ltd., 532, Osaka, Japan aut European Journal of Clinical Pharmacology Springer-Verlag 49/4(1996-01-01), 279-284 0031-6970 49:4<279 1996 49 228 https://doi.org/10.1007/BF00226328 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00226328 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Uematsu T. Department of Pharmacology, Hamamatsu University School of Medicine, 431-31, Hamamatsu, Japan aut NATIONALLICENCE 700 1- Nagashima S. Department of Pharmacology, Hamamatsu University School of Medicine, 431-31, Hamamatsu, Japan aut NATIONALLICENCE 700 1- Inaba H. Department of Pharmacology, Hamamatsu University School of Medicine, 431-31, Hamamatsu, Japan aut NATIONALLICENCE 700 1- Nakashima M. Department of Pharmacology, Hamamatsu University School of Medicine, 431-31, Hamamatsu, Japan aut NATIONALLICENCE 700 1- Kajiho T. Department of Clinical Pharmacology, Fujisawa Pharmaceutical Co. Ltd., 532, Osaka, Japan aut NATIONALLICENCE 700 1- Kageyama H. Department of Clinical Pharmacology, Fujisawa Pharmaceutical Co. Ltd., 532, Osaka, Japan aut NATIONALLICENCE 700 1- Sugiyama A. Department of Clinical Pharmacology, Fujisawa Pharmaceutical Co. Ltd., 532, Osaka, Japan aut NATIONALLICENCE 773 0- European Journal of Clinical Pharmacology Springer-Verlag 49/4(1996-01-01), 279-284 0031-6970 49:4<279 1996 49 228 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer