Constant-rate infusion of nicotine and cotinine. I. A physiological pharmacokinetic analysis of the cotinine disposition, and effects on clearance and distribution in the rat

摘要: The tissue partition of cotinine was measured by a GC-MS method following 6-day constant-rate input nicotine and to male rats means an osmotic minipump. tissue-to-blood coefficients were calculated for adipose (0.08), brain (0.48), heart muscle (0.55), intestinal (0.53), hepatic (0.64), pulmonary (0.50), renal (0.99), skeletal (0.51), the infusion. When infused partitioning increased factor 2.3–4.9, depending on sampled. Another group animals killed at timed intervals from 10 min 30 hr, after having received single intravenous bolus dose 0.5 mg cotinine, washout traced in blood tissues. A physiological model used simulate disposition cotinine. Generally, model-predicted concentrations consistent with those found experimentally. fractional uptake into various tissues simulated. Blood, intestinal, embodied more than 70% total body load drug. Clearance (Cl),volume distribution (Vd),and biological half-life (t1/2)were both infusion study fitting monoexponential iv data rat. Significant differences apparent clearance compared constant rate volume was, however, studies. impact change also