I The pharmacokinetics of dihydroergotamine (DHE) in plasma were examined in six normotensive subjects after single acute doses of dihydroergotamine, 10 ,ug/kg i.v. and 10, 20 and 30 mg orally. 2 The mean apparent half-time of elimination was 2.37 -+-0.29 h and plasma clearance of DHE was 1002 + 169 ml/min. 3 Mean apparent absorption of DHE determined from the 10 mg dose was 26.6 -+-10o and ranged from 8.9 to 60.31/o. The oral bioavailability after the 10, 20 and 30 mg doses averaged 0.47 +(0.07%c, 0.59 +(0. 13%o and 0.52 + 0.14% respectively. Inter-patient variability in bioavailability was 6-fold. 4 The results indicate that pre-systemic 'first-pass' extraction of DHE is the main determinant of its oral bioavailability. Oral doses of the drug up to 30 mg do not saturate this extraction process resulting in apparently linear kinetics for the drug.

The ancient product honey produced by honeybees, particularly the species Apis mellifera from the nectar blossoms or from exudates of trees and plants. Honey contains a very high content of carbohydrates, mostly monoand disaccharides but it also contains many members of the family of antioxidant flavonoids. Over the last several decade of studies on human disease processes it has become recognized that an elevated, unfavourable oxidation status and a states of chronic inflammation underlies multiple diseases most notably, cardiovascular disease (CVD). The underlying cause of most CVD is atherosclerosis, the trapping of lipids in the vessel wall by modified proteoglycans, followed by oxidation, a chronic immune response and the development and rupture of atherosclerotic plaques. Many of the flavonoids present in honey have actions which impact on the oxidative and other processes of atherosclerosis. In this review we describe the actions of many of the flavonoids present in honey and speculate on the manner in which these might aggregate to produce a favorable CVD protective effect of honey per se.