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Use of microdosing to predict pharmacokinetics at the therapeutic dose: Experience with 5 drugs
A volunteer trial was performed to compare the pharmacokinetics of 5 drugs—warfarin, ZK253 (Schering), diazepam, midazolam, and erythromycin—when administered at a microdose or pharmacologic dose.
Exogenous melatonin entrains rhythm and reduces amplitude of endogenous melatonin: An in vivo microdialysis study
The circadian rhythm of melatonin production was studied using on‐line, in vivo microdialysis in the rat pineal gland and three phase markers were calculated, indicating increase (IT50), decrease (DT50) and amplitude of the rhythm.
A microdialysis study on pineal melatonin rhythms in rats after an 8h phase advance: new characteristics of the underlying pacemaker
Using the microdialysis technique to elucidate specific properties of the circadian pacemaking system in the hypothalamus, by measurement of melatonin production in the pineal gland, the system had completely recovered and all animals regained normal rhythmicity, in phase with the new light/dark cycle.
GABA receptors in the region of the dorsomedial hypothalamus of rats are implicated in the control of melatonin and corticosterone release.
The results of this study imply that the SCN can influence the sympathetic outflow of the hypothalamus through its GABA-containing projection, which probably explain the previously reported strong inhibitory effect of benzodiazepines on plasma melatonin in both animals and humans.
Mass balance study of [14C] rabeprazole following oral administration in healthy subjects.
The results support the previous finding that the substantial contribution of the non-enzymatic thioether pathway minimizes the effect of CYP2C19 polymorphism on the inter-individual variation ofplasma clearance of rabeprazole compared with other PPIs.
Melatonin on-line
Novel non-indolic melatonin receptor agonists differentially entrain endogenous melatonin rhythm and increase its amplitude.
Unexpectedly, all melatonin receptor agonists increased the amplitude of melatonin secretion, in clear contrast to entrainment with melatonin, which significantly decreased the amplitude.