Secretory characteristics of the ghrelin profile for the pig are still unknown. Our objective was to clarify the mechanisms that influence ghrelin secretion during differing feeding patterns. Pigs were initially fed a commercial pelleted diet offered ad libitum and blood samples collected for 24 h at intervals of 1 h. The pigs were then entrained for 17 days to a twice daily interval feeding regimen (0900-1000 and 1600-1700 h) and blood samples were collected for 12 h (0800-2000 h). This was followed by a similar interval feeding and blood sampling regimen with the 0900-1000 h feeding period being replaced by a sham feed where pigs were shown their usual feed but none offered. During the ad libitum feeding regimen, there was no preprandial rise or postprandial fall in circulating plasma total ghrelin concentration, which remained constant throughout the sampling period. In addition, no preprandial rise or postprandial fall in ghrelin concentrations was observed when pigs were fed either twice or once daily; however, plasma ghrelin concentration rose gradually over the 12-h sampling period during the twice daily feeding regimen and increased further when pigs were fed once per day. This increase in ghrelin levels coincided with an increase in plasma GH and non-esterified fatty acid concentrations and was not associated with either plasma glucose or insulin concentrations. These results suggest that circulating total plasma ghrelin concentrations in the pig appear to be influenced by chronic changes in energy balance rather than the feeding pattern per se.

Eight patients with arthritis and knee effusions received 13 doses of a single 800-mg ibuprofen tablet every 8 hours. Serum and synovial fluid samples were obtained after the first and last doses and assayed for the R(-) and S(+) enantiomers of ibuprofen by a stereospecific assay. Since only S(+)-ibuprofen inhibits cyclo-oxygenase, a description of the time course of this isomer in synovial fluid is needed for the development of suitable pharmacodynamic models. The isomers were significantly different with respect to peak concentrations and areas under the concentration-time curves (AUC) in synovial fluid levels. No significant accumulation of either isomer was observed in serum or synovial fluid levels between the first and the last doses. The steady-state concentration of both isomers fluctuated less in synovial fluid than in plasma, and the synovial fluid concentrations of the S(+) isomer were about twice that of the R(-) isomer. The mean synovial albumin concentration was about 60% of the serum albumin concentration, and the steady-state isomer AUC values in synovial fluid were significantly correlated with the corresponding serum values after the differences between the two fluids with respect to albumin concentration were corrected. The authors conclude that binding of the isomers to albumin and the serum-synovial fluid albumin ratio controls the steady-state distribution of the ibuprofen isomers into synovial fluid. The ramifications of these findings in the development of satisfactory concentration-response relationships are discussed.