1887
Volume 2010, Issue 1
  • ISSN: 0253-8253
  • E-ISSN: 2227-0426

Abstract

To assess the plasma concentration-time profile of sildenafil alone and after a single dose (400 mg) of cimetidine, with other pharmacokinetic parameters, a study was conducted at the Department of Pharmaco- logy, College of Medicine and Department of Che-mistry, College of Science, University of Mosul, from May 2008-June 2008. Twelve healthy volunteers were each given a sildenafil tablet 50 mg and blood samples were drawn at 0, 0.5,1, 2, 4, 6, 8,10 and 12 hours after administration. After a one week washout period, the same volunteers were given cimetidine 400 mg followed two hours later by sildenafil 50 mg and blood samples drawn at 0, 0.5,1,2, 4, 6, 8,10 and 12 hours after the sildenafil administration. Using high performance liquid chromatography (HPLC) for analysis, the concentration-time profile, half-life (t1 /2), area under the curve (AUC), k (elimination) were measured. Maximum plasma concentration (Cmax) and time to reach maximum plasma concentration (T max) were calculated.

Co-administration of cimetidine resulted in significantly higher plasma concentrations of sildenafil, reflected by a significant rise in AUC (p < 0.0001) and a significant increase in C max (p < 0.0001). The k (elimination) of sildenafil was significantly delayed (p < 0.0001) and the elimination half-life was prolonged (p < 0.0001).

Cimetidine through its action as an inhibitor of Cytochrome P3 A4 (the metabolic pathway of sildenafil) increases the plasma level of sildenafil as reflected by the increase in AUC, C max, 11 /2 and a significant reduction in k(elimination).

Loading

Article metrics loading...

/content/journals/10.5339/qmj.2010.1.7
2010-06-01
2019-10-14
Loading full text...

Full text loading...

References

  1. 1. Ballard   SA., , Gingell   CJ., , Tang   K., , Turner   LA., , Price   ME., , Naylor   AM. . Effect of sildenafil on relaxation of human corpus cavernosum tissue in vitro and on the activities of cyclic nucleotide phosphodiesterase isoenzymes. . J Urol . 1998; ;159: : 2164– 2171 .
    [Google Scholar]
  2. 2. Cheitlin   MD., , Huitter   AM Jr., , Brindis   RG., , Ganz   P., , Kaul   S., , Russell   RO. . Use of Sildenafil (Viagra) in patients with cardiovascular disease. . J Am Coll Cardiol . 1999; ;33: : 273– 282 .
    [Google Scholar]
  3. 3. Warrington   JS., , Shader   RI., , Von Moltke   LL., , Green blatt   DJ. . In vitro biotransformation of sildenafil (Viagra) identification of human cytochrome and potential drug interactions. . Drug Metab Dispos . 2000; ;28: : 392– 397 .
    [Google Scholar]
  4. 4. Hyland   R., , Roe   EG., , Jones   BC., , Smith   DA. . Identification of the cytochrome P450 enzymes involved in the N-demethylation of sildenafil. . Br J Clin Pharmacol . 2001; ;51: : 239– 248 .
    [Google Scholar]
  5. 5. Martinez   C., , Albert   C., , Agandez   JA., , Herrero   E., , Carrillo   JA., , Marquez   M. . Comparative in vitro and in vivo inhibition of cytochrome P450 CYP1A2, CYP2D6, and CYP3A4 by H2 - receptor antagonists. . Clin Pharmacol Therap . 1999; ;65: : 531– 539 .
    [Google Scholar]
  6. 6. Somogy   A., , Gugler   R. . Clinical pharmacokinetics of cimetidine. . Clin Pharmacokinet . 1983; ;8: : 463– 495 .
    [Google Scholar]
  7. 7. Sheu   T., , An -Bang   WU., , Yeh   G-C., , Hsia   A., , Ho   HO. . Development of a liquid chromatographic method for bioanalytical applications with sildenafil. . J Chromatogr B Analyt Technol Biomed Life Sci . 2003; ;Jul: 1-2 : 255– 262 .
    [Google Scholar]
  8. 8. Kling   J. . From hypertension to angina to Viagra. . Mod Drug Discov . 1998; ;1: : 31– 38 .
    [Google Scholar]
  9. 9. Roland   F., , Shariat   K., , Von Wuilmowsky   H., , Bohm   M. . Sildenafil in the treatment of Raynauds phenomenon resistance to vasodilatory therapy. . Circulation . 2005; ;112: 19 : 2980– 2985 .
    [Google Scholar]
  10. 10. Richalet   JP., , Gratadour   P., , Robach   P., , Pharm   I., , Dechaux   M., , Joncquiret-Latarjet   A. , et al. , Sildenafil inhibits altitude-induced hypozemia and pulmonary hypertension. . Am J Respir Crit Care Med . 2005; ;171: 3 : 275– 281 .
    [Google Scholar]
  11. 11. McLellan   RA., , Drobitch   RK., , Monshouwer   M., , Renton   KW. . Fluoroquinolone antibiotics inhibit cytochrome P450 mediated microsomal drug metabolism in rat and human. . Drug Metab Dispos . 1996; ;24: : 1134– 1138 .
    [Google Scholar]
  12. 12. Wilner   K., , Laboy   L., , LeBel   M. . The effect of cimetidine and antacid on the pharmacokinetic profile of sildenafil citrate in healthy male volunteers. . Br J Clin Pharmacol . 2002; ;53: supple : 31S– 36S .
    [Google Scholar]
  13. 13. Hedaya   MA., , El-Afify   DR., , El-Moghraby   GM. . The effect of ciprofloxacin and clarithromycin on sildenafil oral bioavailability in human volunteers. . Biopharm Drug Dispos . 2006; ;27: : 103– 110 .
    [Google Scholar]
  14. 14. Muirhead   GJ., , Walff   MB., , Fielding   A., , Kleinermans   D., , Buss   N. . Pharmacokinetic profile interactions between sildenafil and saquinavir/ ritonavir. . Br J Clin Pharmacol . 2000; ;50: : 99– 107 .
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journals/10.5339/qmj.2010.1.7
Loading
  • Article Type: Research Article
Keyword(s): cimetidine co-administration , serum concentration-time profile and Sildenafil
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error