APPLICATION OF SERUM NICOTINE AND PLASMA COTININE CONCENTRATIONS TO ASSESSMENT OF NICOTINE REPLACEMENT IN LIGHT, MODERATE, AND HEAVY SMOKERS UNDERGOING TRANSDERMAL THERAPY

As part of a clinical trial investigating the level of nicotine replac ement with different doses of transdermal therapy for smoking cessatio n, peak and trough serum nicotine and plasma cotinine concentrations w ere 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-h our patch delivering a transdermal nicotine dose of 0, 11, 22, or 44 m g and stratified bp self-reported smoking rate as either light (10-15 cigarettes per day), moderate (16-30 cigarettes per day), or heavy (>3 0 cigarettes per day). Steady-state concentrations of nicotine and cot inine were attained in 1 and 3 days, respectively, at all doses and we re independent of baseline smoking rate. Mean percentage replacement o f nicotine was calculated by dividing steady-state peak nicotine or co tinine concentrations by their respective baseline concentrations. Sig nificant underreplacement occurred in subjects receiving the 11 mg/day parch regardless of baseline smoking rate. Underreplacement also occu rred in moderate and heavy smokers receiving 22 mg/day and in light sm okers at this same dose. Complete replacement occurred only in subject s receiving the 44 mg/day patch. These results have several implicatio ns for transdermal nicotine therapy. First, with the higher nicotine a nd cotinine levels observed with heavier smoking, it is inherent that one size does not fit all, and were is a need to consider more individ ualization of dosage for nicotine patch therapy. Second, there is subs tantial underreplacement with the 22 mg/day dose in moderate to heavy smokers and in same light smokers. Third, even with twice the usual do se (i.e., 44 mg/day), there was no accumulation of either nicotine or cotinine. Plasma cotinine levels after achievement of steady stare (.e ., after 3 days of patch therapy) can be collected at any time and use d to calculate percent replacement using baseline levels. Journal of C linical pharmacology, 1998;38:502-509 (C) 1998 The American College of Clinical Pharmacology.