RECTAL PHARMACOKINETICS OF BUDESONIDE

The pharmacokinetics and systemic availability of budesonide after rec tal 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 wa s given on a separate occasion. An intravenous administration (0.5 mg) was given as reference. With this design, individual hepatic bypass o f the rectally administered budesonide dose could be estimated. The ph armacokinetics of the two enema formulations were similar, although no t bioequivalent. Mean systemic availability was 16% (range 4.2-43%) an d 15% (3.2-50%) after rectal administration and 6.3% (2.4-10%) after o ral administration. The rectal data revealed a small intra- but a subs tantial inter-subject variability in systemic availability. C-max 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. Absorpti on was rapid and essentially terminated within 3 h after rectal dosing [t(max) = 1.3 h for both formulations (range 0.5-2.0)], but was slowe r after oral dosing [t(max) = 2.1 h (1.0-6.0)]. If a complete absorpti on 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 a fter rectal dosing does not seem to be caused by differences in first- pass liver metabolism but rather by hepatic bypass of a varying portio n of administered drug. This portion seems to be typical for an indivi dual and might be explained by anatomical differences between subjects .