caa a22 4500 477058094 CHVBK 20180405111352.0 cr unu---uuuuu 170330e19960101xx s 000 0 eng 10.1007/BF00226330 doi (NATIONALLICENCE)springer-10.1007/BF00226330 Rectal pharmacokinetics of budesonide [Elektronische Daten] [K. Dahlström, S. Edsbäcker, A. Källén] The pharmacokinetics and systemic availability of budesonide after rectal administration of two single enema doses (2 mg in 100 ml fluid of almost identical composition) were compared in 15 healthy volunteers. In 11 of these subjects, 2 mg oral budesonide in a gelatine capsule was given on a separate occasion. An intravenous administration (0.5 mg) was given as reference. With this design, individual hepatic bypass of the rectally administered budesonide dose could be estimated. The pharmacokinetics of the two enema formulations were similar, although not bioequivalent. Mean systemic availability was 16% (range 4.2-43%) and 15% (3.2-50%) after rectal administration and 6.3% (2.4-10%) after oral administration. The rectal data revealed a small intra- but a substantial inter-subject variability in systemic availability. Cmax was 3.3 nmol·l-1 (0.95-8.2), 3.0 nmol·l-1 (0.64-8.9) and 1.3 nmol·l-1 (0.61-3.0), respectively, for the three formulations. Absorption was rapid and essentially terminated within 3 h after rectal dosing [tmax=1.3 h for both formulations (range 0.5-2.0)], but was slower after oral dosing [tmax=2.1 h (1.0-6.0)]. If a complete absorption after oral and rectal dosing is assumed, the fraction of the rectal dose entering the liver at first pass can be calculated to be 88% (55-99%). The higher systemic availability and intersubject variability after rectal dosing does not seem to be caused by differences in first-pass liver metabolism but rather by hepatic bypass of a varying portion of administered drug. This portion seems to be typical for an individual and might be explained by anatomical differences between subjects. Springer-Verlag, 1996 Budesonide nationallicence enema nationallicence pharmacokinetics nationallicence healthy subjects nationallicence hepatic bypass nationallicence Dahlström K. Department of Human Pharmacology, Clinical Research and Development, Astra Draco AB, Box 34, S-22100, Lund, Sweden aut Edsbäcker S. Department of Human Pharmacology, Clinical Research and Development, Astra Draco AB, Box 34, S-22100, Lund, Sweden aut Källén A. Department of Biostatistics and Data Processing, Astra Draco AB, Lund, Sweden aut European Journal of Clinical Pharmacology Springer-Verlag 49/4(1996-01-01), 293-298 0031-6970 49:4<293 1996 49 228 https://doi.org/10.1007/BF00226330 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00226330 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Dahlström K. Department of Human Pharmacology, Clinical Research and Development, Astra Draco AB, Box 34, S-22100, Lund, Sweden aut NATIONALLICENCE 700 1- Edsbäcker S. Department of Human Pharmacology, Clinical Research and Development, Astra Draco AB, Box 34, S-22100, Lund, Sweden aut NATIONALLICENCE 700 1- Källén A. Department of Biostatistics and Data Processing, Astra Draco AB, Lund, Sweden aut NATIONALLICENCE 773 0- European Journal of Clinical Pharmacology Springer-Verlag 49/4(1996-01-01), 293-298 0031-6970 49:4<293 1996 49 228 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer