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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 56 (2000), S. 293-297 
    ISSN: 1432-1041
    Keywords: Key words Dalteparin ; Low-molecular-weight heparins ; Pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Journal of comparative physiology 167 (1997), S. 328-334 
    ISSN: 1432-136X
    Keywords: Key wordsApical calcium channels ; Nifedipine ; Diltiazem ; Verapamil ; L-channels ; Lanthanum ; Cobalt ; Nickel
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The skin of intact, free-swimming Xenopus laevis transports Ca2+ inwardly in a manner that is proportional to the external [Ca2+] up to about 0.3 mmol · l−1, saturates above 0.3 mmol · l−1, and is opposed to the electrochemical gradient. Efflux is relatively constant at external concentrations between 0.016 and 0.6 mmol · l−1; net flux which is negative below 0.125 mmol · l−1 becomes positive above this external [Ca2+]. Allometric analysis suggests that both Ca2+ influx and efflux scale to the 2/3 power approximately like surface area. There were no significant differences in influx between summer and fall animals; however, efflux was greater in the fall and this resulted in a change from positive balance in the summer to negative balance in the fall. Isolated skins were shown to support a Ca2+ uptake rate of nearly 30 nmol · cm−2 · h−1. The phenylalkylamine verapamil in the apical bathing solution significantly inhibited this at 25 μmol · l−1. The benzothiazepine diltiazem was also effective at 50 μmol · l−1 while the dihydropyradine nifedipine was ineffective up to 100 μmol · l−1. The inorganic ion La3+ was effective at blocking Ca2+ uptake at 300 μmol · l−1; Ni2+ was also effective at 500 μmol · l−1 but Co2+ was ineffective up to 500 μmol · l−1. These results suggest that apical calcium channels in Xenopuslaevis skin have properties similar to mammalian L-channels and fish gill Ca2+ channels.
    Type of Medium: Electronic Resource
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