Tear/plasma urea ratio as a correction coefficient for drug monitoring in tears

Objective: To formulate the tear/plasma urea ratio as a coefficient for correcting drug concentrations in tears. Subjects and Methods: Urea concentrations were measured in 14 paired tear and plasma samples from seven healthy adult volunteers (3 women, 4 men). A second sample was obtained one hour after the first. The samples were simultaneously assayed for urea concentrations by a urease method (Boehringer Mannheim). Results: Our data show a highly significant correlation between tear and plasma urea concentrations in all the samples (r = 0.985, p < 0.001; r = 0.928, p < 0.003; and r = 0.944, p < 0.001 in the first, second, and total collection of samples, respectively). In all paired tear and plasma samples, urea content in tears was higher than in plasma (p < 0.001, p < 0.015, and p < 0.001 in the first, second, and total samples, respectively). The tear/plasma urea ratio in all samples ranged from 1.016 to 1.225 (mean ± SD 1.126 ± 0.068) and had a significant negative correlation (r = -0.538; p < 0.05) with tear volume (range 25-155 μL, mean ± SD 83.9 ± 42.6). Conclusions: Higher urea concentrations in tears than in plasma and a negative correlation between tear volume and the tear/plasma urea ratio indicate that tear evaporation and, consequently, tear concentration occur during sample collection. These data and the highly significant correlation between tear and plasma urea concentrations justify the use of the tear/plasma urea ratio as a correction coefficient for monitoring drug concentrations in tears.