Phenobarbital administration induces calcimimetic resistance and requires parathyroidectomy in secondary hyperparathyroidism hemodialysis patients

Calcimimetics, marketed in 2004, are very effective in the management of patients affected by secondary hyperparathyroidism of chronic kidney disease-mineral bone disorders. During the last years their introduction, improving the quality of life, significantly reduced the indications to a surgical treatment. Cinacalcet hydroclorhide, the most common used calcimimetic drug, is eliminated primarily via oxidative metabolism mediated, in part, through cytochrome P450 (CYP) 3A4. Thus, the potential for an inductor of CYP3A4 to alter the pharmacokinetics of C is of clinical importance. We report herein the cases of two Caucasians epileptic hemodialysis secondary hyperparathyroidism patients, resistant to medical management, in treatment with CYP3A4 inductor (phenobarbital), in which cinacalcet obtained an incomplete effect. In case of pharmacological resistance, as in our patients, atypical relationships between parathyroid glandular hyperplasia and parathyroid hormone secretion may be observed. The use of phenobarbital, or of others CYP3A4 inductors, may alter C pharmacokinetic, reducing the efficacy of medical management of patients affected by secondary hyperparathyroidism. In these clinical conditions, a careful monitoring of parathyroid hormone, calcium serum levels and parathyroid glandular volume is requested to evaluate calcimimetic dose adjustment or an early indication to surgery.