Physiological influences

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. 

Menthol is widely used as a flavorant in foods, mouthwash, toothpaste, and cigarettes. A moderate inhibition of CYP2A6-mediated nicotine metabolism in human 

Clearance of nicotine is decreased in the elderly (age 65) compared to adults (Molander et al. 2001). Total clearance was lower by 23%, and renal clearance lower by 49% in the elderly compared to yonng adults. Lower nicotine metabolism in the elderly may be contribnted to by rednced liver blood flow, since no decrease in CYP2A6 protein levels or nicotine metabolism in liver microsomes due to age has been detected (Messina et al. 1997). No differences in steady-state nicotine plasma levels or estimated plasma clearance valnes were detected in three age gronps (18-39, 40-59, and 60-69 years) nsing patches with the same nicotine content (Gonrlay and Benowitz 1996). The volnme of distribntion of nicotine is lower in older snbjects due to a decrease in lean body mass (Molander et al. 2001). 

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. 

Kidney failure not only decreases renal clearance of nicotine and cotinine, but also metabolic clearance of nicotine (Molander et al. 2000). Metabolic clearance of nicotine is reduced by 50% in subjects with severe renal impairment compared to healthy subjects. It is speculated that accumulation of uremic toxins may inhibit CYP2A6 activity or downregulate CYP2A6 expression in liver. Hepatic metabolism of several drugs is reduced in kidney failure, mainly via downregulation of CYP enzymes and/or inhibition of transporters (Nolin et al. 2003). 

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Francey, R.J., Gifford, R.M., Sharkey, T.D., Weir, B. (1985). Physiological influences on carbon isotope discrimination in huon pine (Lagarostrobes frank-linii). Oecologia, 66, 211-18. 

Physiological influence of metals was assumed from the value and significance of correlation coefficients that are shown in Table 14. 

Transmission through autonomic ganglia is more complex than neurotransmission at the neuromuscular and postganglionic neuroeffector junctions and is subject to numerous pharmacological and physiological influences. In some ganglionic synapses, especially at parasympathetic ganglia, there is a simple presynaptic to postsynaptic cell relationship in others, the presynaptic to postsynaptic cell relationship may involve neurons interposed between the presynaptic and postsynaptic elements (interneurons). 

Banoub M, Tetzlaff JE, Schubert A Pharmacologic and physiologic influences affecting sensory evoked potentials ... 

Mechanism and Physiological Influences of Cereal Gluten on Anatomical Parts of the Small Intestine The Role of Wheat Proteins... 

MECHANISM AND PHYSIOLOGICAL INFLUENCES OF CEREAL GLUTEN ON ANATOMICAL PARTS OF THE SMALL INTESTINE THE ROLE OF WHEAT PROTEINS IN INDUCTION OF OTHER DISEASES (DIARRHEA AND CELIAC DISEASE)... 

Conte M. H., Thompson A., Lesley D., and Harris R. P. (1998a) Generic and physiological influences on the alkenone/ alkenoate versus growth temperature relationship in Emiliania huxleyi and Gephyrocapsa oceanica. Geochim. Cosmo-chim. Acta 62, 51—68. 

Objective differences, when found, are largely due to physiologic influences (blood/body volume and metabolic intrapopulation differences) and less commonly due to ethnic variation. In the United States, an estimate of less than 5% of drugs subject to significant clinical ethnic variation was reported by participating companies in a US A/PMA Survey (Edwards, 1991) and confirmed by the retrospective surveys undertaken for ICH 2 (Harvey and Walker, 1993 Natio and Yasuhova, 1993). 

The level of serum iron is the concentration of iron bound to transferrin. Normahy, transferrin is abont one-third bound (saturated) to iron. Unfortunately, the serum iron level of many patients with IDA remains within the lower hmits of normal, as it takes a considerable amount of time to deplete iron stores, giving a false-negative test result. There is also a 20% to 30% diurnal variation in serum iron levels (higher in the moriung, lower in the afternoon) as well as a 20% to 25% day-to-day variation among individuals. Variability results from technical and physiologic influences. Serum iron levels are decreased by infection and inflammation. Consequently, as a diagnostic tool, serum iron levels are best interpreted in conjunction with the TIBC. The serum iron... 

The extrauterine exposure to drug in rodents may differ from that of intrauterine exposure in nonhuman primates because metabolic mechanism could differ in the extrauterine situation especially if the drug is being administered orally, and physiological influences will differ between the intrauterine and extrauterine situation, for example, pulmonary versus placental oxygen supply, nutrient supply, or different kidney function. 

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