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Effect of Dose and Ointment Application Technique on Nitroglycerin Plasma Concentrations
Author(s) -
Iafrate R. Peter,
Yost Richard L.,
Curry Stephen H.,
Gotz Vincent P.,
Caranasos George J.
Publication year - 1983
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1002/j.1875-9114.1983.tb03232.x
Subject(s) - chemistry , pharmacokinetics , plasma concentration , area under the curve , confidence interval , absorption (acoustics) , dosing , high performance liquid chromatography , chromatography , anesthesia , medicine , materials science , composite material , organic chemistry
Each of ten non‐smoking, healthy male volunteers between the ages of 20 and 30 and within 10% of their ideal body weight received four nitroglycerin ointment (NTG‐O) treatments: ½″ NTG‐O over 3.94 in 2 and 7.88 in 2 , and 1″ NTG‐0 over 3.94 in 2 and 7.88 in 2 in a randomized order. Eleven blood samples and 22 determinations of heart rate and blood pressure were obtained over each 6‐hour study period. Nitroglycerin plasma concentrations were determined by gas‐liquid chromatography with electron capture detection. Area under the nitroglycerin plasma concentration‐time curve (AUC), peak plasma concentration (C max ), and time to peak concentration (T max ) were determined for each study. C max and AUC values were corrected for the actual dose applied. Differences between AUC, C max and T max were tested using repeated measures analysis of variance. Change in surface area had no statistically significant effect on AUC, C max and T max . Mean AUC for the ½″ and 1″ doses differed (648 vs 2003 ng.ml −1 min, p = 0.016), as did C max (4.6 vs 12.4 ng.ml −1 , p = 0.022); however, there was no correlation between individual doses and AUCs. Generally, NTG plasma concentrations within the proposed therapeutic range of 1.2–11.1 ng.ml −1 were detectable throughout each study interval. These data suggest that continuous absorption occurred throughout the 6‐hour dosing interval, that a trend toward increased AUC and C max occurred with the larger surface area, and that, in general, doubling the dose of NTG‐O doubles the AUC.