Nicotine blood concentration

The blood concentrations resnlting from a standard infusion rate of 9 mg kg day result are almost identical concentrations to those that have been measured in heavy smokers, smoking at their ad lib rate (Benowitz et al. 1982 LeSage et al. 2002). Of course, one difference is that, in the smokers case, the levels decline during daily sleep. On the other hand, it is difficnlt to argue that a week of continuous nicotine exposure results in an nnrealistically high amount of total nicotine exposnre, as compared to years of 16 or 17 h per day of continuously elevated nicotine blood concentrations in hnman heavy smokers. 

The relationship between nicotine intake and steady state cotinine blood levels can be expressed in the following way, based on steady state exposnre conditions Dnic = CLcot X CcoT f, where Dnic is the intake (dose) of nicotine, CLcot is the clearance of cotinine, Ccot is the steady state blood concentration of cotinine and f is the fraction of nicotine converted to cotinine. On rearranging the equation, Dnic = (CLcot f) x Ccot = K x Ccot where K is a constant that converts a given blood level of cotinine to nicotine intake. On average, K = 0.08 mg 24h ng ml (range 0.05-1.1, CV = 21.9%). Thus, a cotinine level of 30 ng ml in blood corresponds on average to a nicotine intake of 24 mg per day. 

F%.1 Venous blood concentrations in nanograms of nicotine per miUimeter of blood as a function of time for various nicotine delivery systems. Data on the cigarette delivering about 1 mg nicotine (filled square), oral snuff delivering 3.6 mg (filled circle), and 4 mg nicotine gum (star) are from those published by Benowitz et al. (1988). Data on 1 mg nicotine nasal spray (filled triangle) are from Schneider et al. (1996). Data on 21 mg transdermal nicotine patch (open square) are from Benowitz (1993). Data on the 4 mg nicotine lozenge (open circle) are from Choi et al. (2003)... 

Blood concentrations of nicotine in individuals who smoked cigarettes, chewed nicotine gum or received nicotine by transdermal patch. 

Toxicity. Nicotine is highly toxic and, in acute poisoning, death may occur within a few minutes due to respiratory failure arising from paralysis of the respiratory muscles. The lethal dose for an adult is between 40 and 60 mg. Blood concentrations greater than 5 pg/ml may be fatal. The maximum permissible atmospheric concentration is 0.5 mg/m. ... 

Nicotine is readily absorbed through the oral mucosa and the lungs. Peak blood concentrations are achieved within 30 seconds of a puff of a cigarette. 

A scheme in which nicotinamide was used as a precursor of NAD was described before the presently accepted biosynthetic pathway for NAD was elucidated. It is not certain whether nicotinamide can serve as a precursor of NAD. The administration of small amounts of nicotinic acid leads to a marked increase in NAD coenzyme levels in the blood. In contrast, the intake of high doses of nicotinamide has little effect on the blood concentration of NAD. Such results may be interpreted two ways either nicotinic acid is a better precursor for NAD coenzymes than nicotinamide, or the conversion of nicotinamide to the coenzyme is restrained. 

It has been suggested that through its effects on (1) rumen fermentation (some experiments have shown increased microbial growth and increased propionic acid production) and (2) cell metabolism (increased utilisation of carbohydrate and reduced lipid mobilisation), nicotinic acid may be a useful supplement to dairy cows, particularly in situations of subclinical ketosis. However, the experimental evidence is not consistent. Nicotinic acid does not always give positive responses in the rumen and increases in blood concentrations were not observed in all experiments. Current recommendations do not advocate the supplementation of dairy cow diets in order to increase milk yield and composition. 

Dehvery via a transdermal patch provides a sustained plasma nicotine concentration, typically lower than venous blood concentrations after tobacco smoking (Figure 122.2). On the other hand, a nasal spray and a vapor inhaler provide immediate 10-fold higher arterial blood concentrations immediately following inhalation compared to venous concentrations after a nicotine patch application. 

Fig. 2 Blood nicotine concentrations during and after cigarette smoking for 9 min, oral snuff (2.5 g), chewing tobacco (average 7.9 g), and nicotine gum (two 2-mg pieces). Average values for 10 subjects ( SEM). Reprinted from Benowitz et al. (1988) with permission from American Society for Clinical Pharmacology and Therapeutics...

An implication of the high degree of hepatic extraction is that clearance of nicotine should be dependent on liver blood flow. Thus, physiological events, such as meals, posture, exercise, or drugs perturbing hepatic blood flow, are predicted to affect the rate of nicotine metabolism. Meals consumed during a steady state infusion of nicotine result in a consistent decline in nicotine concentrations, the maximal effect seen 30-60 min after the end of a meal (Gries et al. 1996 Lee et al. 1989). Hepatic blood flow increases about 30% and nicotine clearance increases about 40% after a meal. 

Neonates have diminished nicotine metabolism, as demonstrated by a nicotine half-life of three to four times longer in newborns exposed to tobacco smoke than in adnlts (Dempsey et al. 2000). Cotinine half-life is reported to be similar in neonates, older children, and adults in two studies (Dempsey et al. 2000 Leong et al. 1998). Other studies found that the half-life of urine cotinine was about three times longer in children less than one year old than to the cotinine half-life in adults (Collier et al. 1994). Urine cotinine half-life can be influenced by variations in urine volume and excretion of creatinine. The study by Dempsey et al. was the only one in which the half-life of cotinine was calculated based on both the blood and urine cotinine concentrations (Dempsey et al. 2000). In that study, both the blood and urine half-lives were similar to adult values, supporting the notion that neonates have the same cotinine half-life as older children and adults. 

Plasma nicotine samples showed no difference dne to body weight in blood nicotine concentration following active patch pretreatment, as expected, confirming eqnal dosing across snbjects. 

Benowitz NL, Kuyt F, Jacob P 3rd (1982) Circadian blood nicotine concentrations during cigarette smoking. CUn Pharmacol Ther 32 758-764... 

Nicotine nasal spray is marketed as a pharmacy-only medication in the UK, and is available only by prescription in the USA. The nasal spray was designed to deliver doses of nicotine to the smoker more rapidly than other NRT products. The device is a multidose bottle with a pump that delivers 0.5 mg of nicotine per 50-pL squirt. Each dose consists of two squirts, one to each nostril. Nicotine from the nasal spray is absorbed into the blood more rapidly than from the gum (Schneider et al. 1996). Venous plasma concentrations after a single 1-mg dose range between 5 and 12 ng mL Time to peak plasma concentration (7j ax) with nasal administration is around 11-13 min for 1-mg doses. This rise time is slower than for cigarette delivery (Henningfield et al. 1993), but faster than for the other NRT products. 

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