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In previous mammalian studies on the role of nicotine in the adverse effects of tobacco smoking on circulation, including on uterine circulation, and fetal development, there were major limitations: (1) routes of nicotine delivery, e.g., oral application, intraperitoneal (i.p.), intravenous (i.v.) injections, or subcutaneous osmotic pump, resulted in nicotine blood PK distinctly different from human smoking, including the rapidity of absorption, rise time and peak of arterial blood concentrations, which determine the magnitude of some cardiovascular effects of nicotine 9

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