rifampin and Hypertension--Pulmonary

A premature twin of 1.9 kg had mitral valve endocarditis develop during neonatal intensive care. Vegetation involving the entire anterior mitral valve leaflet was identified. Reconstruction was achieved by near complete resection of the anterior mitral valve leaflet and retention of the peripheral margin of coaptation including primary and secondary chordae. The body of the anterior mitral valve leaflet was reconstructed using fresh autologous pericardium, a technique not previously reported in an infant of this size. Three and a half years later, the child is well and has required no further intervention.

Topics: Bioprosthesis; Birth Weight; Captopril; Combined Modality Therapy; Diseases in Twins; Diuretics; Endocarditis, Bacterial; Female; Gentamicins; Humans; Hypertension, Pulmonary; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Methicillin Resistance; Mitral Valve; Mitral Valve Insufficiency; Pericardium; Rifampin; Staphylococcal Infections; Transplantation, Autologous; Twins, Monozygotic; Vancomycin

The tuberculostatic compound rifampin (INN, rifampicin) induces the expression of a number of drug metabolism-related genes involved in multidrug resistance (P-glycoprotein and multidrug resistance proteins 1 and 2), cytochromes (cytochrome P450 [CYP] 3A4), uridine diphosphate-glucuronosyltransferases, monoamine oxidases, and glutathione S -transferases. Drugs that depend on these enzymes for their metabolism are prone to drug interactions when coadministered with rifampin. A novel, clinically relevant drug interaction is described between rifampin and mycophenolate mofetil (MMF), a cornerstone immunosuppressive molecule used in solid organ transplantation. Long-term rifampin therapy caused a more than twofold reduction in dose-corrected mycophenolic acid (MPA) exposure (dose-interval area under the concentration curve from 0 to 12 hours [AUC 0-12]) when administered simultaneously in a heart-lung transplant recipient, whereas subsequent withdrawal of rifampin resulted in reversal of these changes after 2 weeks of washout (dose-corrected AUC 0-12 after rifampin withdrawal, 19.7 mg.h.L-1.g -1 versus 6.13 mg.h.L-1.g-1 before rifampin withdrawal [221% change]; dose-uncorrected AUC 0-12 after rifampin withdrawal, 29.6 mg.h/L [daily MMF dose, 3 g] versus 18.4 mg.h/L [daily MMF dose, 6 g] during rifampin administration [60.8% change]). Failure to recognize this drug interaction could potentially lead to MPA underexposure and loss of clinical efficacy. The effect of rifampin on MPA metabolism can, at least in part, be explained by simultaneous induction of renal, hepatic, and gastrointestinal uridine diphosphate-glucuronosyltransferases and organic anion transporters with subsequent functional inhibition of enterohepatic recirculation of MPA.

Topics: Area Under Curve; Chronic Disease; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Interactions; Drug Therapy, Combination; Enterohepatic Circulation; Glucuronosyltransferase; Heart-Lung Transplantation; Histiocytosis, Langerhans-Cell; Humans; Hypertension, Pulmonary; Male; Metabolic Clearance Rate; Middle Aged; Mycophenolic Acid; Pharmacology, Clinical; Respiratory Insufficiency; Rifampin; Tacrolimus; Time Factors; Uridine Diphosphate; Withholding Treatment