Premium
Inhibition of ex vivo neutrophil activation by oral LY293111, a novel leukotriene B 4 receptor antagonist
Author(s) -
MARDER P.,
SPAETHE S. M.,
FROELICH L. L.,
CERIMELE B. J.,
PETERSEN B. H.,
TANNER T.,
LUCAS R. A.
Publication year - 1996
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1996.tb00008.x
Subject(s) - ex vivo , placebo , medicine , antagonist , in vivo , dosing , dose–response relationship , pharmacology , receptor , biology , pathology , alternative medicine , microbiology and biotechnology
1 The effects of orally administered LY293111 on ex vivo neutrophil Mac‐1 upregulation were determined in a total of 24 healthy male subjects within three study periods. 2 In the first period, eight volunteers received 60 mg LY293111 or placebo three times daily in 22 total doses over 8 days followed by a 1 week follow‐up. The average ex vivo Mac‐1 response of the LY293111 group was 56% of the pre‐dose control (95% confidence interval (CI) 44.3 to 67.9%; P <0.01). The inhibitory effect was maximum at the end of dosing and had disappeared by day 14. 3 In the second period, eight subjects received 120 mg LY293111 or placebo three times daily in 22 total doses over 8 days followed by a 1 week follow‐up. The average response of the LY293111 group was 70% of the pre‐dose control (95% CI 59.7 to 81.0%; P <0.01). The inhibitory effect was maximum the day following the initial dose and continued throughout the dosing period. 4 In the third period, eight subjects received 200 mg LY293111 or placebo twice daily in 15 total doses over 8 days followed by a 1 week follow‐up. Mac‐1 upregulation was 64% of pre‐dose levels (95% CI 53.8 to 75.1%; P <0.01) over the course of the study period. The inhibition had disappeared 2 days following the final dose. Alternate neutrophil stimulation by fMLP was not inhibited. 5 No statistically significant inhibition was observed for placebo‐treated subjects. 6 No statistically significant differences were apparent between the active dose regimens. 7 The results indicate that orally administered LY293111 is pharmacologically active in humans. Results from this study may be useful in determining dose selection for efficacy trials.