The effect of the co-administration of the H|2-receptor antagonists on the pharmacokinetics and pharmacodynamics of the H|1-receptor antagonists in rabbits
| dc.contributor.author | Naas, Fatma Moftah | en_US |
| dc.date.accessioned | 2007-05-15T15:15:16Z | |
| dc.date.available | 2007-05-15T15:15:16Z | |
| dc.date.issued | 1996-09-01T00:00:00Z | en_US |
| dc.degree.discipline | Chemistry | en_US |
| dc.degree.level | Doctor of Philosophy (Ph.D.) | en_US |
| dc.description.abstract | The effect of the co-administration of the H$\sb2$-receptor antagonists cimetidine, famotidine and ranitidine, and the antifungal agent ketoconazole, on the pharmacokinetics and pharmacodynamics of the H$\sb1$-receptor antagonist hydroxyzine and its active metabolite cetirizine in rabbits was evaluated by measuring hydroxyzine and cetirizine serum concentrations by HPLC and using suppression of the histamine-induced wheal to evaluate the peripheral antihistaminic effects of these compounds. The co-administration of cimetidine inhibited the elimination of hydroxyzine and cetirizine so that increased serum concentrations of these H$\sb1$-receptor antagonists were achieved, compared to serum concentrations observed when hydroxyzine was administered alone. Co-administration of cimetidine resulted in enhanced suppression of the histamine-induced wheal formation. This effect may be due both to increased serum H$\sb1$-antagonist concentrations and to the direct inhibition of cimetidine on the H$\sb2$-receptors of the skin vasculature. The co-administration of famotidine and ranitidine had no effect on the pharmacokinetics of hydroxyzine and cetirizine, resulting in serum concentrations similar to those obtained when hydroxyzine was administered alone. However, the co-administration of both famotidine and ranitidine resulted in enhanced suppression of the histamine-induced wheal formation. This effect may be due to the direct inhibition of famotidine and ranitidine on the H$\sb2$-receptors on the skin vasculature. The co-administration of ketoconazole, an antifungal agent which has an inhibitory effect on the hepatic cytochrome P-450 enzyme system, delayed the elimination of both hydroxyzine and cetirizine, yielding increased serum concentrations compared to those obtained when hydroxyzine was administered alone. The enhanced suppression of the histamine-induced wheal formation following ketoconazole co-administration was probably due to the increased serum H$\sb1$-antagonist concentrations, since ketoconazole has no effect on H$\sb1$- or H$\sb2$-receptors. The elimination of cetirizine from patients with primary biliary cirrhosis (PBC) was prolonged but renal clearance of unmetabolized drug was reduced when compared to results obtained in healthy volunteers. The suppression of the histamine-induced wheals and flares was also enhanced and prolonged. Doses of cetirizine may need to be adjusted in patients with PBC. | en_US |
| dc.format.extent | 9734021 bytes | |
| dc.format.extent | 184 bytes | |
| dc.format.mimetype | application/pdf | |
| dc.format.mimetype | text/plain | |
| dc.identifier.uri | http://hdl.handle.net/1993/736 | |
| dc.language.iso | eng | en_US |
| dc.rights | open access | en_US |
| dc.title | The effect of the co-administration of the H|2-receptor antagonists on the pharmacokinetics and pharmacodynamics of the H|1-receptor antagonists in rabbits | en_US |
| dc.type | doctoral thesis | en_US |