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. 1990 Jun;100(2):195–200. doi: 10.1111/j.1476-5381.1990.tb15781.x

SK&F S-106203 inhibits leukotriene C4, leukotriene D4 and leukotriene E4 vasopressor responses in the conscious rat.

E F Smith 3rd 1, M J Slivjak 1, J W Egan 1, R D Eckardt 1, J F Newton 1
PMCID: PMC1917428  PMID: 2165834

Abstract

1. The purpose of these experiments was to investigate the effects of the selective peptidoleukotriene receptor antagonist, SK&F S-106203, on leukotriene C4 (LTC4), LTD4 and LTE4 vasopressor responses in the conscious, normotensive rat. SK&F S-106203 was administered as a bolus followed by a continuous infusion in order to provide information on the relationship between antagonism of leukotriene responses and steady-state plasma concentrations. 2. Infusion of SK&F S-106203 at doses of 0.2 mgkg-1 + 1 mgkg-1 h-1, 1 mgkg-1 + 3 mgkg- h-1 or 2 mgkg-1 + 10 mgkg-1 h-1 produced dose-dependent steady-state plasma drug concentrations of 1.0, 3.2 and 23.8 micrograms ml-1, respectively. Plasma SK&F S-106203 concentrations appeared to increase in a linear fashion at doses of 1 and 3 mgkg-1 h-1; at the highest dose the increment in plasma drug concentrations (i.e., 7-8 fold) was greater than the increment in dose (i.e., 3 fold), suggesting saturation of the primary clearance mechanism(s) at this dose. 3. SK&F S-106203 (2 mgkg-1 + 10 mgkg-1 h-1) had no effect on noradrenaline-, vasopressin-, isoprenaline-, or U 46619-induced responses. 4. SK&F S-106203 produced dose-dependent rightward shifts in the LTC4 and LTE4 dose-response curves.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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