Study objectives included determination of the maximum tolerated dose ( MTD ) and dose-limiting toxicity ( DLT ) under normal and mildly hypoxic conditions , and following co-administration with steady-state sildenafil , assessment of nitrite pharmacokinetics , and evaluation of the fraction exhaled nitric oxide ( FENO ) and concentrations of iron-nitrosyl hemoglobin ( Hb ( Fe ) - NO ) and S-nitrosothiols ( R-SNO ) as biomarkers of local and systemic NO exposure , respectively .