caa a22 4500 477057292 CHVBK 20180405111350.0 cr unu---uuuuu 170330e19960601xx s 000 0 eng 10.1007/s002280050117 doi (NATIONALLICENCE)springer-10.1007/s002280050117 Plasma and skin suction-blister-fluid pharmacokinetics and time course of the effects of oral mizolastine [Elektronische Daten] [O. Chosidow, C. Dubruc, P. Danjou, E. Fuseau, E. Espagne, G. Bianchetti, J. P. Thenot, S. Herson, P. Rosenzweig, J. Revuz] Objective:To investigate plasma and skin suction-blister-fluid pharmacokinetics of oral mizolastine in order to determine whether the drug concentration in the fluid of suction-induced skin blisters could better predict the antihistamine activity than the plasma concentration. Setting: Department of Internal Medicine, Université Paris 6. Subjects: Ten healthy male volunteers. Methods: The volunteers (mean age 26.8 years, mean weight 75.8 kg) received a single 10-mg oral dose of mizolastine at 1000 hours. The pharmacokinetic study included 11 plasma and 9 blister fluid samples and blister epidermal-roof specimens. Mizolastine was assayed by high-performance liquid chromatography (HPLC). Each volunteer also received nine intradermal injections of 5 μg histamine. Antihistamine activity was assessed as the post-treatment percentages of changes in the histamine-induced relative wheal and flare areas versus baseline. Results: Mizolastine mean Cmax (SD) and median tmax were, respectively, 380 ng ⋅ ml−1and 0.8 h in plasma, and 21.8 ng ⋅ ml−1 and 10 h in blister fluid. Mizolastine could not be quantified in the epidermis. The maximal histamine-induced relative flare inhibition was 72.5% and was attained at the median time of 3 h post-dosing and therefore was delayed by 2.2 h with respect to the plasma tmax. Mean relative wheal inhibition, although lower, showed the same time profile. A direct relationship could not be found between drug concentrations in blister fluid and antihistamine activity. Simulated concentrations in the peripheral compartment better explain the maximum inhibition effect on flare, observed 3 h post-dosing, with a flatter hysteresis loop obtained when plotting relative flare inhibition versus plasma or blister-fluid drug concentrations. Conclusion: The mizolastine concentrations in the skin suction-blister fluid were not predictive of the antihistamine activity. Springer-Verlag Berlin Heidelberg, 1996 Key words Mizolastine nationallicence H1-receptor antagonist nationallicence antihistamine nationallicence skin suction-blister fluid nationallicence histamine-induced wheal and flare nationallicence Chosidow O. Department of Internal Medicine, Hôpital de la Salpêtrière, Université Paris 6, 47 bd de l' Hôpital, F-75651 Paris Cedex 13, France, FR aut Dubruc C. Clinical Pharmacokinetics and Clinical Pharmacology, Synthélabo Recherche (LERS), Bagneux, France, FR aut Danjou P. Clinical Pharmacokinetics and Clinical Pharmacology, Synthélabo Recherche (LERS), Bagneux, France, FR aut Fuseau E. Clinical Pharmacokinetics and Clinical Pharmacology, Synthélabo Recherche (LERS), Bagneux, France, FR aut Espagne E. Department of Dermatology, Hôpital Henri-Mondor, Créteil, France, FR aut Bianchetti G. Clinical Pharmacokinetics and Clinical Pharmacology, Synthélabo Recherche (LERS), Bagneux, France, FR aut Thenot J. P. Clinical Pharmacokinetics and Clinical Pharmacology, Synthélabo Recherche (LERS), Bagneux, France, FR aut Herson S. Department of Internal Medicine, Hôpital de la Salpêtrière, Université Paris 6, 47 bd de l' Hôpital, F-75651 Paris Cedex 13, France, FR aut Rosenzweig P. Clinical Pharmacokinetics and Clinical Pharmacology, Synthélabo Recherche (LERS), Bagneux, France, FR aut Revuz J. Department of Dermatology, Hôpital Henri-Mondor, Créteil, France, FR aut https://doi.org/10.1007/s002280050117 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s002280050117 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Chosidow O. Department of Internal Medicine, Hôpital de la Salpêtrière, Université Paris 6, 47 bd de l' Hôpital, F-75651 Paris Cedex 13, France, FR aut NATIONALLICENCE 700 1- Dubruc C. Clinical Pharmacokinetics and Clinical Pharmacology, Synthélabo Recherche (LERS), Bagneux, France, FR aut NATIONALLICENCE 700 1- Danjou P. Clinical Pharmacokinetics and Clinical Pharmacology, Synthélabo Recherche (LERS), Bagneux, France, FR aut NATIONALLICENCE 700 1- Fuseau E. Clinical Pharmacokinetics and Clinical Pharmacology, Synthélabo Recherche (LERS), Bagneux, France, FR aut NATIONALLICENCE 700 1- Espagne E. Department of Dermatology, Hôpital Henri-Mondor, Créteil, France, FR aut NATIONALLICENCE 700 1- Bianchetti G. Clinical Pharmacokinetics and Clinical Pharmacology, Synthélabo Recherche (LERS), Bagneux, France, FR aut NATIONALLICENCE 700 1- Thenot J. P. Clinical Pharmacokinetics and Clinical Pharmacology, Synthélabo Recherche (LERS), Bagneux, France, FR aut NATIONALLICENCE 700 1- Herson S. Department of Internal Medicine, Hôpital de la Salpêtrière, Université Paris 6, 47 bd de l' Hôpital, F-75651 Paris Cedex 13, France, FR aut NATIONALLICENCE 700 1- Rosenzweig P. Clinical Pharmacokinetics and Clinical Pharmacology, Synthélabo Recherche (LERS), Bagneux, France, FR aut NATIONALLICENCE 700 1- Revuz J. Department of Dermatology, Hôpital Henri-Mondor, Créteil, France, FR aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer