Systemic levels of glyceryl trinitrate following topical application to the anoderm do not correlate with the measured reduction in anal pressure

Background. Topical 0.2 per cent glyceryl trinitrate (GTN) lowers resting a nal pressure (RAP) and heals two-thirds of chronic anal fissures. Over 50 p er cent of patients experience headache, presumably through systemic absorp tion, but the pharmacokinetics; of GTN ointment are unknown. This study eva luated the systemic absorption profile of GTN, and correlation between plas ma GTN levels, RAP, haemodynamic variables and side-effects. Methods: Thirty healthy volunteers were recruited with local medical school ethics committee approval. Continuous static anal manometry was performed for 10 min before and 2 h after application of 0.2 per cent GTN (0-5 g) to the anoderm. Blood samples were taken from an intravenous cannula, and puls e and blood pressure were measured before application of GTN, and 10, 20, 3 0, 40, 50, 60, 90, 120 and 180 min thereafter. Details of side-effects were recorded. Results: GTN was detected in the plasma 10 min to 3 h after topical applica tion. RAP was significantly reduced after 10 rain, but had returned to pret reatment values by 120 min. Pulse was statistically unchanged during the st udy; systolic blood pressure was significantly lower 20-90 min after GTN ap plication, and diastolic pressure was decreased throughout the study. Heada ches were experienced by 14 of 30 volunteers after a median (range) of 41 ( 4-120) min, persisting for 74 (30-176) min, with an intensity score of 19 ( 5-30) mm represented on a 100-mm linear visual analogue scale. There was no correlation between plasma GTN concentration, RAP, and the onset, duration or intensity of headaches. Conclusion: Topical GTN acts locally on the internal anal sphincter; system ic levels do not contribute significantly to the reduction in RAP. There is marked interindividual variation in plasma GTN levels, and no correlation with haemodynamic variables and side-effects.