title: Systemic levels of glyceryl trinitrate following topical application to the anoderm do not correlate with the measured reduction in anal pressure.
abstract: BACKGROUND
  Topical 0.2 per cent glyceryl trinitrate (GTN) lowers resting anal pressure (RAP) and heals two-thirds of chronic anal fissures. Over 50 per cent of patients experience headache, presumably through systemic absorption, but the pharmacokinetics of GTN ointment are unknown. This study evaluated the systemic absorption profile of GTN, and correlation between plasma 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 pulse and blood pressure were measured before application of GTN, and 10, 20, 30, 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 application. RAP was significantly reduced after 10 min, but had returned to pretreatment values by 120 min. Pulse was statistically unchanged during the study; systolic blood pressure was significantly lower 20-90 min after GTN application, and diastolic pressure was decreased throughout the study. Headaches 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.
  
  
  CONCLUSIONS
  Topical GTN acts locally on the internal anal sphincter; systemic 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.
authors.affiliation: Department of Surgery, University of Nottingham, Nottingham, UK.
authors.forename: M
authors.initials: M
authors.lastname: Jonas
authors.forename: D A
authors.initials: DA
authors.lastname: Barrett
authors.forename: P N
authors.initials: PN
authors.lastname: Shaw
authors.forename: J H
authors.initials: JH
authors.lastname: Scholefield
mesh_terms: D000042:Absorption; D000287:Administration, Topical; D000328:Adult; D000368:Aged; D001003:Anal Canal / Q000378:metabolism*; D001794:Blood Pressure / Q000502:physiology; D005260:Female; D006261:Headache / Q000139:chemically induced; D006801:Humans; D008297:Male; D008365:Manometry; D008875:Middle Aged; D005996:Nitroglycerin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D009824:Ointments; D011312:Pressure; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D009824:Ointments; D014665:Vasodilator Agents; D005996:Nitroglycerin