Application of Serum Nicotine and Plasma Cotinine Concentrations to Assessment of Nicotine Replacement in Light, Moderate, and Heavy Smokers Undergoing Transdermal Therapy

Abstract

As part of a clinical trial investigating the level of nicotine replacement with different doses of transdermal therapy for smoking cessation, peak and trough serum nicotine and plasma cotinine concentrations were measured in 70 subjects while they were actively smoking (baseline) and daily for 6 consecutive inpatient days while they were receiving transdermal nicotine. Subjects were randomly assigned to a daily 24-hour patch delivering a transdermal nicotine dose of 0, 11, 22, or 44 mg and stratified by self-reported smoking rate as either light (10-15 cigarettes per day), moderate (16-30 cigarettes per day), or heavy (>30 cigarettes per day). Steady-state concentrations of nicotine and cotinine were attained in 1 and 3 days, respectively, at all doses and were independent of baseline smoking rate. Mean percentage replacement of nicotine was calculated by dividing steady-state peak nicotine or cotinine concentrations by their respective baseline concentrations. Significant underreplacement occurred in subjects receiving the 11 mg/day patch regardless of baseline smoking rate. Underreplacement also occurred in moderate and heavy smokers receiving 22 mg/day and in light smokers at this same dose. Complete replacement occurred only in subjects receiving the 44 mg/day patch. These results have several implications for transdermal nicotine therapy. First, with the higher nicotine and cotinine levels observed with heavier smoking, it is inherent that one size does not fit all, and there is a need to consider more individualization of dosage for nicotine patch therapy. Second, there is substantial underreplacement with the 22 mg/day dose in moderate to heavy smokers and in some light smokers. Third, even with twice the usual dose (i.e., 44 mg/day), there was no accumulation of either nicotine or cotinine. Plasma cotinine levels after achievement of steady state (i.e., after 3 days of patch therapy) can be collected at any time and used to calculate percent replacement using baseline levels.

A study of the consequences of early gestational ethanol and/or nicotine exposure in the mouse

“…The average serum cotinine concentrations (172 and 179 ng/ml) obtained in this study are similar to that measured in humans who self-report consuming 10 -15 cigarettes per day, defined as light smokers (Lawson et al, 1998). Two similar models of oral ad libitum access to freebase nicotine at a concentration of 100 µg/ml in female C57BL/6 have been previously reported.…”

“…It is possible, that should DNA methylation be assayed on a genome-wide scale, that more extensive DNA methylation changes may be identified -some of which may persist into postnatal life and and in turn be associated with the changes in postnatal growth. The findings from this thesis demonstrate the capacity for nicotine (at a dosage equivalent to smoking 10 -15 cigarettes per day [Lawson et al, 1998]) to have both molecular and phenotypic consequences in the offspring, raising questions as to the safety of nicotine usage during early 103 pregnancy. Further work is required both in animal models and humans in order to better characterise not only these phenotypic consequences, but also the underlying molecular mechanisms.…”

Nicotine and oxidative cigarette smoke constituents induce immune-modulatory and pro-inflammatory dendritic cell responses

“…Since the alkaloid nicotine is a pharmacologically active component of CSE, we first tested if nicotine concentrations attained in CSE (or within the range of clinically-relevant nicotine levels (Lawson et al, 1998)) could stimulate CXCL8/IL-8 generation by human DCs. To determine this, immature human DCs were incubated with 0.01-10 µg/ml nicotine for 12-18 hours, and CXCL8 levels were subsequently determined by ELISA.…”

The functional mu opioid receptor (OPRM1) Asn40Asp variant predicts short-term response to nicotine replacement therapy in a clinical trial

“…53 These time points were selected to coincide with a period of regular smoking and after steadystate cotinine levels from treatment were achieved. 53 Cotinine levels were analyzed by gas chromatography with nitrogen phosphorus detection, modified for analysis using a capillary GC column. 54 …”