Arterial-venous plasma concentration differences of 6-chloro-2-pyridylmethyl nitrate in humans after sublingual...

The plasma concentrations of 6-chloro-2-pyridylmethyl nitrate after sublingual administration were determined in six healthy male volunteers (venous plasma) and eleven patients (arterial plasma) with ischemic heart failure. The pharmacokinetics of the compound was investigated in volunteers. Plasma concentration-time data in each volunteer were found to fit a two-compartment open model with zero-order absorption. The pharmacokinetic parameters estimated from curve-fitting the plasma concentration-time data were as follow: Tmax 10 +/- 2.8 min, Cmax 8.16 +/- 2.48 ng/mL and CLP 6.16 +/- 1.79 L/min (means +/- S.D.). The arterial plasma concentrations (11.9 +/- 5.14 ng/mL) 7 min after sublingual administration were significantly higher (p less than 0.05) than those in venous samples (6.86 +/- 2.80 ng/mL). These results support that the arterial-venous gradient exists after administration of 6-chloro-2-pyridylmethyl nitrate in humans.