Evaluation of the effect of candesartan cilexetil on the steady-state pharmacokinetics of tacrolimus in renal transplant patients

• Published in: Biopharmaceutics & drug disposition Vol. 26; no. 4; pp. 135 - 141
• Main Authors: Pietruck, Frank, Kiel, Gerhard, Birkel, Manfred, Stahlheber-Dilg, Bodo, Philipp, Thomas
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.05.2005; Wiley
• Subjects: Administration, Oral; Adult; Antihypertensive Agents - administration & dosage; Antihypertensive Agents - pharmacology; Antihypertensive Agents - therapeutic use; Benzimidazoles - administration & dosage; Benzimidazoles - pharmacology; Benzimidazoles - therapeutic use; Biological and medical sciences; Biological Availability; Biphenyl Compounds - administration & dosage; Biphenyl Compounds - pharmacology; Biphenyl Compounds - therapeutic use; Blood Pressure - drug effects; candesartan cilexetil; Creatinine - analysis; Drug Administration Schedule; drug interaction; Drug Interactions; Female; Graft Rejection - prevention & control; Humans; Hypertension - drug therapy; Hypertension - metabolism; Immunosuppressive Agents - administration & dosage; Immunosuppressive Agents - pharmacokinetics; Immunosuppressive Agents - therapeutic use; Kidney Transplantation; Male; Medical sciences; Metabolic Clearance Rate; Middle Aged; Pharmacology. Drug treatments; tacrolimus; Tacrolimus - administration & dosage; Tacrolimus - pharmacokinetics; Tacrolimus - therapeutic use; Tetrazoles - administration & dosage; Tetrazoles - pharmacology; Tetrazoles - therapeutic use; Human; Evaluation; Tetrazole derivatives; Cilexetil; Candesartan; Peptide hormone; Lactone; Transplantation; AT1 angiotensin receptor; Macrolide; Kidney; candesartan cilexetil; Octapeptide; Renin angiotensin system; Urinary system; Tacrolimus; Benzimidazole derivatives; Biphenyl derivatives; Antihypertensive agent; Drug interaction; Angiotensin antagonist; Immunosuppressive agent; Angiotensin II; Pharmacokinetics
• ISSN: 0142-2782; 1099-081X
• DOI: 10.1002/bdd.440

Background. Candesartan cilexetil is a possible treatment for hypertension in renal allograft recipients. Tacrolimus is widely used as an immunosuppressant following renal transplantation. The aim of this study was to evaluate the effect of multiple doses of candesartan cilexetil on the steady‐state pharmacokinetics of tacrolimus. Methods. Twelve patients received oral doses of tacrolimus twice daily for 12 days from study day −2 until day 10, single oral doses of candesartan cilexetil placebo on study days −2 to −1, single oral doses of 2 mg candesartan cilexetil once daily on study days 1 to 3, oral doses of 4 mg candesartan cilexetil once daily on study days 4 to 6, and oral doses of 16 mg candesartan cilexetil once daily on study days 7 to 9. Serial blood samples were collected on days −1, 6 and 9 and were analysed for tacrolimus using microparticle enzyme immunoassay. Results. Mean Cmax,ss and AUCτ,ss values for tacrolimus on day 6 (4 mg candesartan) and day 9 (16 mg candesartan cilexetil) were similar to those on day −1 (tacrolimus alone). Renal function did not change under treatment with candesartan cilexetil compared with baseline. The co‐administration of multiple oral doses of cardesartan cilexetil with oral doses of tacrolimus was well tolerated. Conclusions. Concomitant administration of multiple doses of candesartan cilexetil does not alter the steady‐state pharmacokinetics of tacrolimus. Copyright © 2005 John Wiley & Sons, Ltd.