title: A pharmacokinetic interaction between clarithromycin and sirolimus in kidney transplant recipient.
abstract: Bacterial infection is a frequent event in renal transplant recipients and often requires the use of antimicrobial agents. In this paper it is reported an evidence of pharmacokinetic interaction between clarithromycin and sirolimus in a kidney transplanted woman, suffering from pulmonary infection sustained by a bacterial pathogen, in particular Hemophilus Influenzae. In the present case report, the concomitant administration of clarithromycin and sirolimus determined impressive increase of sirolimus trough blood concentrations from 6.2 up to 54 ng/mL and this increase was associated with an acute impairment of renal function, almost completely reversed upon both drugs discontinuation. This drug-drug interaction is due to a likely inhibition of activity of both cytochrome P450 3A4 and P-glycoprotein. Although this interaction could be predicted, it represents the first reported clinical evidence.
authors.affiliation: Department of Neurosciences, Section of Clinical Pharmacology, School of Medicine, Federico II University of Naples, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Capone
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Palmiero
authors.forename: Antonio
authors.initials: A
authors.lastname: Gentile
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Basile
authors.forename: Stefano
authors.initials: S
authors.lastname: Federico
authors.forename: Massimo
authors.initials: M
authors.lastname: Sabbatini
authors.forename: Maria
authors.initials: M
authors.lastname: Potenza
authors.forename: Anna
authors.initials: A
authors.lastname: Perfetti
authors.forename: Maria
authors.initials: M
authors.lastname: Pieri
authors.forename: Giovanni
authors.initials: G
authors.lastname: Tarantino
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000208:Acute Disease; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017291:Clarithromycin / Q000494:pharmacology*; D051544:Cytochrome P-450 CYP3A; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006193:Haemophilus influenzae; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D007674:Kidney Diseases / Q000139:chemically induced; D016030:Kidney Transplantation; D008875:Middle Aged; D012141:Respiratory Tract Infections / Q000188:drug therapy / Q000382:microbiology; D020123:Sirolimus / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000900:Anti-Bacterial Agents; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; D003577:Cytochrome P-450 Enzyme System; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D017291:Clarithromycin; D020123:Sirolimus