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Digitale Medien

The effect of body weight on dalteparin pharmacokinetics A preliminary study (2000)

Yee, J. Y. V. ; Duffull, S. B.

Springer

European journal of clinical pharmacology 56 (2000), S. 293-297

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ISSN: 1432-1041

Schlagwort(e): Key words Dalteparin ; Low-molecular-weight heparins ; Pharmacokinetics

Quelle: Springer Online Journal Archives 1860-2000

Thema: Chemie und Pharmazie , Medizin

Notizen: Abstract Aim: To investigate whether there were significant differences in the volume of distribution (V) and clearance (CL) of dalteparin in obese versus normal-weight patients, and thereby determine whether dosing of dalteparin should be based on total body weight, lean body weight or an adjusted body weight in obese patients. Methods: Patients (ten obese and ten normal weight) treated with dalteparin were matched for age, gender, lean body weight and creatinine CL. Two steady-state plasma dalteparin concentrations were taken from each patient and assayed in duplicate. The pharmacokinetic values of V and CL were estimated, for each patient, using the Bayesian maximum a posteriori method with the program ABBOTTBASE. Results: The mean V in obese patients was approximately 60% larger than in normal-weight patients, but this was not statistically significant (P=0.11; two-tailed). The mean value of V (8.4 l) in the normal-weight patients was similar to that reported in the literature. The mean difference in values of CL (18% larger in obese patients) was not clinically or statistically significant. A poor correlation was seen between V and lean body weight (r 2=0.05). There was a moderate correlation between V and total body weight (r 2=0.52) and between V and adjusted body weight (r 2=0.55); adjusted body weight=[lean body weight + 0.4(total body weight – lean body weight)]. Total body weight and adjusted body weight provided a better correlation with CL (r 2=0.39, 0.32, respectively) than did lean body weight (r 2=0.01). Conclusion: These results suggest that doses of dalteparin in obese patients should be based on total body weight or an adjusted body weight, but not lean body weight. This study highlights some potential differences in the pharmacokinetics of dalteparin in individuals who are obese, and further work is necessary to quantify these differences in more detail.

Materialart: Digitale Medien

URL: http://dx.doi.org/10.1007/s002280000141

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Digitale Medien

Hypophysial portal vascular infusion of TRH in the rat: An ultrastructural and radioimmunoassay studySupported in part by NIH Biomedical Research Support Grant RR05420 to the Medical University of South Carolina and by the South Carolina State Appropriation for Biomedical Research. (1978)

Wilbur, D. L. ; Yee, J. A. ; Raigue, S. E.

New York, NY [u.a.] : Wiley-Blackwell

American Journal of Anatomy 151 (1978), S. 277-293

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ISSN: 0002-9106

Schlagwort(e): Life and Medical Sciences ; Cell & Developmental Biology

Quelle: Wiley InterScience Backfile Collection 1832-2000

Thema: Medizin

Notizen: The hypophysial portal vessels and anterior pituitary gland of adult male Wistar rats were exposed surgically. A hypophysial portal vessel was cannulated and infused for one minute with saline or thyrotrophin (TRH). Anterior pituitary glands were collected at 1, 5, 15, 30, or 60 minutes after cessation of infusion, for light and electron microscopic examination. Before and immediately after cannulation of a portal vessel, a 1-ml sample of blood was collected at 1, 5, 15, 30, or 60 minutes, from the femoral vein for radioimmunoassay (RIA) of growth hormone. Thyrotrophs from anterior pituitary glands of rats infused with TRH displayed emiocytic activity at all time-periods studied. Rough endoplasmic reticular (RER) cisternae were dilated at 15 minutes following infusion and remained dilated at 30 and 60 minutes. TRH was observed to stimulate emiocytic activity in most pituitary cell-types. Extensive dilations of RER cisternae were also observed in mammotrophs and gonadotrophs, but were not observed in somatotrophs or adrenocorticotrophs. The demonstration that thyrotrophs, mammotrophs, somatotrophs, and gonadotrophs respond to TRH suggests that some common features may be shared by these cells. Preliminary analysis of the RIA data show that TRH was potent in elevating radioimmunoassayable growth hormone levels. Significant increases (p 〈 0.02) in plasma GH levels were present at the earlier time periods studied (1, 5, and 15 minutes) following the infusion of TRH, but not at 30 or 60 minutes. These findings provide additional support for the non-specific action of TRH upon the various adenohypophysial cell types, and demonstrate that TRH stimulates these cells by a direct action on the adenohypophysis.

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