Microdosing of a Carbon-14 Labeled Protein in Healthy Volunteers Accurately Predicts Its Pharmacokinetics at Therapeutic Dosages.

Preclinical development of new biological entities (NBEs), such as human protein therapeutics, requires considerable expenditure of time and costs. Poor prediction of pharmacokinetics in humans further reduces net efficiency. In this study, we show for the first time that pharmacokinetic data of NBEs in humans can be successfully obtained early in the drug development process by the use of microdosing in a small group of healthy subjects combined with ultrasensitive accelerator mass spectrometry (AMS).

Automated combustion accelerator mass spectrometry for the analysis of biomedical samples in the low attomole range.

The increasing role of accelerator mass spectrometry (AMS) in biomedical research necessitates modernization of the traditional sample handling process. AMS was originally developed and used for carbon dating, therefore focusing on a very high precision but with a comparably low sample throughput. Here, we describe the combination of automated sample combustion with an elemental analyzer (EA) online coupled to an AMS via a dedicated interface.

Participation of beta-adrenergic receptors on macrophages in modulation of LPS-induced cytokine release.

For several years it is known that beta-adrenergic receptor agonists have anti-inflammatory effects. However, little is known about the role of beta-adrenergic receptors on macrophages in the modulation of cytokine production by beta-agonists during inflammation. In this study, the presence of beta-receptors on PMA-differentiated U937 human macrophages, and the participation of these receptors in the modulation of LPS-mediated cytokine production by beta-agonists was investigated.

Retention of 14C label is lower in old than in young Wistar rats after oral dosing with [14C]pyridoxine.

Ten young (6-mo-old) and ten old (31-mo-old) male Wistar rats fed a purified diet (250 g casein and 6 mg pyridoxine.HCl per kg) from weaning were given either a single oral dose or five repeated oral doses of 14C-labeled pyridoxine. At various times after dosing animals of each age group were killed.

Influence of age and sex on vitamin B-6 vitamer distribution and on vitamin B-6 metabolizing enzymes in Wistar rats.

Vitamin B-6 vitamer distribution and activities of vitamin B-6 metabolizing enzymes were evaluated in aging male and female Wistar rats fed a purified diet (containing 250 g of casein and 6 mg of pyridoxine hydrochloride per kg) from weaning until 31 mo of age. Plasma pyridoxal 5'-phosphate (PLP) concentration became lower with increasing age, with the largest decrease in the 1st yr of life. An age-related change in vitamin B-6 distribution between the various tissues examined was observed: B-6 vitamer content increased in heart and brain, whereas PLP content decreased in gastrocnemius muscle, kidney and liver.