Pharmacokinetic studies of various preparations of glyceryl trinitrate

Abstract

1 The pharmacokinetics and pharmacodynamics of five pharmaceutical preparations of glyceryl trinitrate (GTN) have been studied in six healthy volunteers. 2 Peak plasma GTN levels of 1.4 +/- 0.1 ng/ml were achieved at 3 min after sublingual administration (0.5 mg); 2.8 +/- 0.6 ng/ml and 2.5 +/- 0.3 ng/ml at 2 h and 4 h after Nitrocontin (6.4 mg) and Sustac (6.4 mg) respectively; 2.7 +/- 0.1 ng/ml and 2.5 +/- 0.2 ng/ml at 30 min after the cream (23 mg) and ointment (35 mg) respectively. 3 The mean times to reach half peak plasma GTN levels were 4.2 +/- 0.7 min after sublingual GTN, 6.5 +/- 0.9 h after Nitrocontin, 4.1 +/- 0.7 h after Sustac, 46.1 +/- 10.2 min after the ointment and 50.2 +/- 39.2 min after the cream. 4 Plasma nitrate (NO3) levels were undetectable after sublingual administration; peak NO3 levels were 0.48 +/- 0.03 microgram/ml at 4 h after Nitrocontin, 0.45 +/- 0.02 microgram/ml at 6 h after Sustac, 0.68 +/- 0.04 microgram/ml at 6 h (end of study) after the ointment and 0.63 microgram/ml at 4 h after the cream. 5 Plasma nitrite (NO2) was undetectable after sublingual GTN and peak NO2 levels were 0.48 +/- 0.04 microgram/ml at 2 h after Nitrocontin, 0.48 +/- 0.02 microgram/ml at 2 h after Sustac, 0.69 +/- 0.02 microgram/ml at 1 h after the ointment and 0.64 +/- 0.02 microgram/ml at 1 h after the cream. 6 Blood pressure (BP) declined throughout the 11 min of the study after sublingual GTN but did not change significantly after Nitrocontin or Sustac. After the ointment and the cream BP fell to the lowest level 30-60 min after administration and remained low throughout the 6 h of the study. 7 Heart rate (HR) increased to a maximum 5 min after sublingual administration with no significant increase after Nitrocontin or Sustac. After the ointment and the cream HR increased gradually to a maximum 30-60 min after administration remaining high throughout the rest of the study.