title: Involvement of CYP 3A5 In the Interaction Between Tacrolimus and Nicardipine: A Case Report.
abstract: Tacrolimus is a calcineurin inhibitor primarily metabolized by CYP3A4 and secondarily by CYP3A5. Several drugs can modify tacrolimus blood levels as calcium channel blockers (CCBs). Interaction with nicardipine was reported in some cases. A man with a history of malignant arterial hypertension treated with nicardipine, underwent kidney transplantation. After transplantation, he was treated with tacrolimus, mycophenolate mofetil and corticoids. Therapeutic drug monitoring of tacrolimus was done regularly showing a mean trough concentration (C0) of 24.39 ng/mL with some concentrations reaching 52 ng/mL. After changing nicardipine by prazosine, the first tacrolimus C0 after stopping nicardipine was 3.2 ng/mL. Increase of tacrolimus trough concentrations is due to the inhibition of CYP3A4. Very high levels of tacrolimus suggest the non expression of CYP3A5. Thus, because of the possible lack of the secondary pathway, therapeutic drug monitoring of tacrolimus is highly recommended at the introduction of CCBs and also at its stopping.
authors.forename: Mouna B
authors.initials: MB
authors.lastname: Sassi
authors.affiliation: Department of Clinical Pharmacology- National Center of Pharmacovigilance, Tunis, 9 Avenue Dr. Zouheir Essafi. 1006 Tunis-Tunisia, Tunisia. gaiesemna@yahoo.fr.
authors.forename: Emna
authors.initials: E
authors.lastname: Gaies
authors.forename: Issam
authors.initials: I
authors.lastname: Salouage
authors.forename: Sameh
authors.initials: S
authors.lastname: Trabelsi
authors.forename: Mohamed
authors.initials: M
authors.lastname: Lakhal
authors.forename: Anis
authors.initials: A
authors.lastname: Klouz
mesh_terms: D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001711:Biotransformation; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000009:adverse effects*; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism*; D065692:Cytochrome P-450 CYP3A Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D004347:Drug Interactions; D016903:Drug Monitoring; D057915:Drug Substitution; D006801:Humans; D006973:Hypertension / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009529:Nicardipine / Q000008:administration & dosage / Q000009:adverse effects*; D019338:Polypharmacy; D011224:Prazosin / Q000008:administration & dosage; D016559:Tacrolimus / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D065692:Cytochrome P-450 CYP3A Inhibitors; D007166:Immunosuppressive Agents; D009529:Nicardipine; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D016559:Tacrolimus; D011224:Prazosin