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, ρ < 0.001; r = 0.928, ρ < 0.003; and r = 0.944, ρ < 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, ρ < 0.015, and ρ < 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 ± S D 1.126 ± 0.068) and had a significant negative correlation (r =-0.538; ρ < 0.05) with tear volume (range 25-155 pL, 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 plasm