Celiprolol double-peak occurrence and gastric motility: Nonlinear mixed effects modeling of bioavailability data obtained in dogs

Investigation of the underlying mechanism leading to inter- and intrasubject variations in the plasma concentration-time profiles of drugs (1) can considerably benefit rational drug therapy. The significant effect of gastric emptying on the rate and extent of celiprolol absorption and its role with respect to double-peak formation was demonstrated in the present study. In four dogs racemic celiprolol was dosed perorally in a crossover design during four different phases of the fasted-state gastric cycle and gastric motility was recorded simultaneously using a manometric measurement system. Intravenous doses were also given to obtain disposition and bioavailability parameters. The blood samples were assayed by a stereoselective HPLC method (2). The time to onset of the active phase of the gastric cycle showed an excellent correlation with the time to celiprolol peak concentration. Furthermore, bioavailability was increased when celiprolol was administered during the active phase. Double peaks were observed when the first active phase was relatively short, suggesting that a portion of the drug remained in the stomach until the next active phase. Population pharmacokinetic modeling of the data with a two-compartment open model with two lag times incorporating the motility data confirmed the effect of time to gastric empyting on the variability of the oral pharmacokinetics of celiprolol. The fasted-state motility phases determine the rate and extent of celiprolol absorption and influence the occurrence of double peaks. Peak plasma levels of celiprolol exhibit less variability if lag times, and therefore gastric emptying times, are taken into consideration.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45049/1/10928_2006_Article_BF02354285.pd

Zlíchovian faunas with early ammonoids from Morocco and their use for the correlation of the eastern Anti-Atlas and the western Dra Valley

Two sections were sampled and measured at Mdâour-El-Kbîr (Dra Valley, western Anti-Atlas) and at eastern Ouidane Chebbi (Tafilalt, eastern Anti-Atlas). In situ elements of two partially limonitized and one carbonatic fauna were found in both sections. We report this fauna from the upper Merzâ-Akhsaď Formation and the lower Mdâour-el-Kbîr Formation at Mdâour-el-Kbîr for the first time. Based on these faunas, we recorded a correlation of the early Emsian (Zlíchovian) strata in the Tafilalt and the Dra Valley regions, which are about 350 km apart. Additionally, new ammonoid finds (Teicherticeras cf. senior, Lenzites gesinae, Weyeroceras angustus) are figured and described including the stratigraphic context. The diagnoses of Lenzites gesinae and Weyeroceras angustus are emended. Tabulate corals (Michelinia mdaourensis sp. nov., Petridictyum sp.) found in both the Tafilalt and Dra Valley are figured and described for the first time

[Persistence of microlamellar Favositids (Cnidaria, Tabulata) in the Devonian]

The structural and microstructural study of some devonian 'Favosites' shows the persistence of the microlamellar species related to Paleofavosites until the lower Eifelian. The evolution of the wall is characterized by an increase of the size of the microlamellae and the substitution of the granules of the median dark line by fiber-like units. (C) Academie des sciences/Elsevier, Paris

Découverte de vertébrés quaternaires à l'entrée de l'Aber-Ildut

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Tectonique du dévonien inférieur de la presqu'île de Crozon : La coupe des Capucins en Roscanvel (massif armoricain, France)

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Douarnenez, 309

Tiré à partNational audienc

Douarnenez, 309

Tiré à partNational audienc

Brest, 57

Tiré à partNational audienc