Pharmacokinetics of anorectal nifedipine and lidocaine (lignocaine) ointment following haemorrhoidectomy: An open-label, single-dose, phase IV clinical study

Clinical Drug Investigation

Volumn 29, Issue 4, 2009, Pages 243-256

  Perrotti, Pasquale ^a,e   Dominici, Patrizia ^b   Grossi, Enzo ^b   Antropoli, Carmine ^a   Giannotti, Guglielmo ^c   Cusato, Maria ^d   Regazzi, Mario ^d   Cerutti, Renata ^b  

^a CARDARELLI HOSPITAL   (Italy)

^b Bracco SpA   (Italy)

^c General Hospital of Crema   (Italy)

^d FONDAZIONE IRCCS POLICLINICO SAN MATTEO   (Italy)

^e NONE   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

ANALGESIC AGENT; ANTROLIN; LIDOCAINE; LIDOCAINE PLUS NIFEDIPINE; UNCLASSIFIED DRUG;

ADULT; AGED; ANUS; AREA UNDER THE CURVE; ARTICLE; BLOOD ANALYSIS; BLOOD PRESSURE; CLINICAL ARTICLE; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DRUG ABSORPTION; DRUG SAFETY; ECG ABNORMALITY; ELECTROCARDIOGRAM; FEMALE; HEART ARRHYTHMIA; HEART RATE; HEMODYNAMICS; HEMORRHOIDECTOMY; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; MALE; MAXIMUM PLASMA CONCENTRATION; NEUROTOXICITY; OINTMENT; OPEN STUDY; PATIENT MONITORING; PHASE 4 CLINICAL TRIAL; POSTOPERATIVE CARE; POSTOPERATIVE PAIN; PRIORITY JOURNAL; SINGLE DRUG DOSE; TIME TO MAXIMUM PLASMA CONCENTRATION; WOUND DRESSING;

ADMINISTRATION, TOPICAL; ADULT; AGED; ANAL CANAL; ANESTHETICS, LOCAL; AREA UNDER CURVE; BLOOD PRESSURE; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; DRUG COMBINATIONS; ELECTROCARDIOGRAPHY; FEMALE; HEART RATE; HEMORRHOIDS; HUMANS; LIDOCAINE; MALE; MIDDLE AGED; NIFEDIPINE; OINTMENTS; VASODILATOR AGENTS;

EID: 62949176494     PISSN: 11732563     EISSN: None     Source Type: Journal    
DOI: 10.2165/00044011-200929040-00003     Document Type: Article

References (43)

1. Nisar PJ, Scholefield JH. Managing haemorrhoids. BMJ 2003; 327: 847-51
2. Goldstein ET, Williamson PR, Larach SW. Subcutaneous morphine pump for postoperative hemorrhoidectomy pain management. Dis Colon Rectum 1993; 36: 439-46
3. Carapeti E, Kamm M, McDonald P, et al. Double-blind randomised controlled trial of effect of metronidazole on pain after day-case haemorrhoidectomy. Lancet 1998; 351: 169-72
4. Wasvary HJ, Hain J, Mosed-Vogel M, et al. A randomized, prospective, double-blind, placebo-controlled trial of effect of nitroglycerin ointment on pain after hemorrhoidectomy. Dis Colon Rectum 2001; 44: 1069-73
5. Deutsch AA, Moshkovitz M, Nudelman I, et al. Anal pressure measurements in the study of hemorrhoid etiology and their relation to treatment. Dis Colon Rectum 1987; 30: 855-7
6. Roe AM, Bartolo DC, Vellacott KD, et al. Submucosal versus ligation excision haemorrhoidectomy: a comparison of anal sensation, anal sphincter manometry and postoperative pain and function. Br J Surg 1987; 74: 948-51
7. Kanellos I, Zacharakis E, Christoforidis E, et al. Usefulness of lateral internal sphincterotomy in reducing postoperative pain after open hemorrhoidectomy. World J Surg 2005; 29: 464-8
8. Goligher JC, Graham NG, De Dombal FT, et al. The value of stretching of anal sphincters in the relief of pain after haemorrhoidectomy [abstract]. Br J Surg 1969; 56: 390
9. Ho YH, Seow-Choen F, Low JY, et al. Randomised controlled trial of trimebutine (anal sphincter relaxant) for pain after haemorrhoidectomy. Br J Surg 1997; 84: 377-9
10. Davies J, Duffy D, Boyt N, et al. Botulinum toxin (botox) reduces pain after hemorrhoidectomy: results of a double-blind, randomized study. Dis Colon Rectum 2003; 46: 1097-102
11. Nicholson TJ, Armstrong D. Topical metronidazole (10 percent) decreases posthemorrhoidectomy pain and improves healing. Dis Colon Rectum 2004; 47: 711-6
12. Vinson-Bonnet B, Coltat JC, Fingerhut A, et al. Local infiltration with ropivacaine improves immediate postoperative pain control after hemorrhoidal surgery. Dis Colon Rectum 2002; 45: 104-8
13. Coskun A, Duzgun SA, Uzunkoy A, et al. Nitroderm TTS® band application for pain after hemorrhoidectomy. Dis Colon Rectum 2001; 44: 680-5
14. Colak T, Akca T, Dirlik M, et al. Micronized flavonoids in pain control after hemorrhoidectomy: a prospective randomized controlled study. Surg Today 2003; 33: 828-32
15. Elton C, Sen P, Montgomery AC. Initial study to assess the effects of topical glyceryl trinitrate for pain after haemorrhoidectomy. Int J Surg Investig 2001; 2: 353-7
16. Chrysos E, Xynos E, Tzovaras G, et al. Effect of nifedipine on rectoanal motility. Dis Colon Rectum 1996; 39: 212-6
17. Antropoli C, Perrotti P, Rubino M, et al. Nifedipine for local use in conservative treatment of anal fissures: preliminary results of a multicenter study. Dis Colon Rectum 1999; 42: 1011-5
18. Ezri T, Susmallian S. Topical nifedipine vs. topical glyceryl trinitrate for treatment of chronic anal fissure. Dis Colon Rectum 2003; 46: 805-8
19. Perrotti P, Antropoli C, Noschese G, et al. Topical nifedipine for conservative treatment of acute haemorrhoidal thrombosis. Colorectal Dis 2000; 2: 18-21
20. Cook TA, Brading AF, Mortensen NJ. Effects of nifedipine on anorectal smooth muscle in vitro. Dis Colon Rectum 1999; 42: 782-7
21. Cook TA, Brading AF, Mortensen NJ. Differences in contractile properties of anorectal smooth muscle and the effects of calcium channel blockade. Br J Surg 1999; 86: 70-5
22. Perrotti P, Bove A, Antropoli C, et al. Topical nifedipine with lidocaine ointment versus active control for treatment of chronic anal fissure: results of a prospective, randomized, double-blind study. Dis Colon Rectum 2002; 45: 1468-75
23. Perrotti P, Antropoli C, Molino D, et al. Conservative treatment of acute thrombosed external hemorrhoids with topical nifedipine. Dis Colon Rectum 2001; 44: 405-9
24. Perrotti P, Grumetto L, Barbato F, et al. Serum levels and possible haemodynamic effects following anorectal application of an ointment containing nifedipine and lignocaine: a study in healthy volunteers. Clin Drug Invest 2006; 26: 459-67
25. Raemsch KD, Sommer J. Pharmacokinetics and metabolism of nifedipine. Hypertension 1983; 5: 18-24
26. Traube M, Hongo M, McAllister Jr RG, et al. Correlation of plasma levels of nifedipine and cardiovascular effects after sublingual dosing in normal subjects. J Clin Pharmacol 1985; 25: 125-9
27. Kurosawa S, Kurosawa N, Owada E, et al. Rectal administration of nifedipine: hemodynamic effects and pharmacokinetics in hypertensives. J Int Med Res 1987; 15: 121-7
28. Kleinbloesem CH, van Harten J, de Leede LG, et al. Nifedipine kinetics and dynamics during rectal infusion to steady state with an osmotic system. Clin Pharmacol Ther 1984; 36: 396-4
29. Covino BG. Toxicity of local anesthetic agents. Acta Anaesthesiol Belg 1988; 39 (3 Suppl. 2): 159-64
30. Tucker GT. Clinical pharmacokinetics of local anesthetics. Clin Pharmacokinet 1979; 4: 241-78
31. Echizen H, Eichelbaum M. Clinical pharmacokinetics of verapamil, nifedipine and diltiazem. Clin Pharmacokinet 1986 Nov; 11 (6): 425-49
32. Covino BG. Pharmacology of local anesthetics. Br J Anaesth 1986; 58: 701-16
33. Tonsuwannont W, Praisontarangkul OA, Manorot M, et al. Pharmacokinetics of oral lidocaine and nifedipine in patients with liver cirrhosis. J Med Assoc Thai 1996 May; 79 (5): 309-19
34. Hardman JG, Limbird LE, Molinoff PB, et al. Goodman & Gilman's the pharmacological basis of therapeutics. 9th ed. New York: McGraw-Hill, 1996: 1195; 1754-65
35. Shiau JM, Su HP, Chen HS, et al. Use of a topical anesthetic cream (EMLA) to reduce pain after hemorrhoidectomy. Reg Anesth Pain Med 2008; 33: 30-5
36. Vickers ER, Marziani N, Gerzina TM, et al. Pharmacokinetics of EMLA cream 5% application to oral mucosa. Anesth Prog 1997; 44: 32-7
37. Leopold A, Wilson S, Weaver JS, et al. Pharmacokinetics of lidocaine delivered from a transmucosal patch in children. Anesth Prog 2002; 49: 82-7
38. Jensen SL. Treatment of first episodes of acute anal fissure: prospective randomised study of lignocaine ointment versus hydrocortisone ointment or warm sitz baths plus bran. Br Med J (Clin Res Ed) 1986; 3 (292): 1167-9
39. McDonald P, Driscoll AM, Nicholls RJ. The anal dilator in the conservative management of acute anal fissures. Br J Surg 1983; 70: 25-6
40. Neiger A, Herms E. The symptomatic therapy of hemorrhoids and anal eczema: a report of experiences from proctology practice. Schweiz Rundsch Med Prax 1990; 79 (31-32): 918-20
41. Brown AC, Sumfest JM, Rozwadowski JV. Histopathology of the internal anal sphincter in chronic anal fissure. Dis Colon Rectum 1989; 32: 680-3
42. Benfeldt E, Serup J, Menné T. Effect of barrier perturbation on cutaneous salicylic acid penetration in human skin: in vivo pharmacokinetics using microdialysis and non-invasive quantification of barrier function. Br J Dermatol 1999; 140: 739-48
43. Jonas M, Barrett DA, Shaw PN, et al. Systemic levels of glyceryl trinitrate following topical application to the anoderm do not correlate with the measured reduction in anal pressure. Br J Surg 2001; 88: 1613-6