caa a22 4500 47581858X CHVBK 20180406123816.0 cr unu---uuuuu 170329e20000701xx s 000 0 eng 10.1007/s002280000142 doi (NATIONALLICENCE)springer-10.1007/s002280000142 Effect of hospitalisation on liver enzymes in healthy subjects [Elektronische Daten] [H. Narjes, G. Nehmiz] Objectives: The aims of the present evaluation were to determine whether the elevations in liver enzymes observed in phase-I trials are more common in subjects being hospitalised than in ambulatory subjects and to assess the relevance of these elevations. We therefore investigated the effect of hospitalisation on liver enzyme levels in subjects of all phase-I trials of sufficient length performed at the two Human Pharmacology Centres of Boehringer Ingelheim, located in Biberach and Ingelheim, Germany, over a 10-year period. Methods: The evaluation was based on 29 phase-I trials conducted between 1987 and 1996. These trials consisted of at least 4 days of observation of 220 subjects on placebo treatment in 273 trial participations. The mean changes (transformed into reference ranges) in the liver enzymes alkaline phosphatase, gamma glutamyl transpeptidase, aspartate aminotransferase, alanine aminotransferase and the AST/ALT ratio of hospitalised subjects were compared with those of ambulatory subjects. Results: A small but statistically significant increase in the mean of the parameters GGT, AST and ALT during phase-I trials was observed in hospitalised subjects compared with ambulatory subjects. The increases were: 8% of the reference range width for GGT, 8% for AST and 17% for the ALT, although the differences were small in absolute terms. A relevant increase (defined as an increase to above the reference range or by at least 50% of the reference range) was more common in hospitalised subjects. Conclusion: Hospitalisation, although it is believed to protect subjects from confounding environmental factors, can itself be associated with increases in liver enzyme levels. The definition of a relevant increase can be used to identify subjects who need further evaluation. The cause of the increase in liver enzyme levels remains unclear. Springer-Verlag Berlin Heidelberg, 2000 Key words Phase-I study nationallicence Liver enzymes nationallicence Placebo treatment nationallicence Narjes H. Human Pharmacology Centre, Boehringer Ingelheim Pharma KG, D-88397 Biberach an der Riss, Germany e-mail: hans-hermann.narjes@bc.boehringer-ingelheim.com Tel.: +49-7351-547472; Fax: +49-7351-542181, DE aut Nehmiz G. Medical Data Services/Biometrics, Boehringer Ingelheim Pharma KG, D-88397 Biberach an der Riss, Germany, DE aut https://doi.org/10.1007/s002280000142 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s002280000142 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Narjes H. Human Pharmacology Centre, Boehringer Ingelheim Pharma KG, D-88397 Biberach an der Riss, Germany e-mail: hans-hermann.narjes@bc.boehringer-ingelheim.com Tel.: +49-7351-547472; Fax: +49-7351-542181, DE aut NATIONALLICENCE 700 1- Nehmiz G. Medical Data Services/Biometrics, Boehringer Ingelheim Pharma KG, D-88397 Biberach an der Riss, Germany, DE aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer