Osteomalacia in an HIV-infected man receiving rifabutin, a cytochrome P450 enzyme inducer: a case report.
BACKGROUND
People infected with human immunodeficiency virus are frequently treated with medications that can induce or inhibit cytochrome P450 enzymes.


METHODS
A 59 year old man treated with zidovudine, lamivudine, indinavir, and ritonavir for infection with human immunodeficiency virus volunteered to take part in a study of bone loss. He was found to have vitamin D insufficiency with secondary hyperparathyroidism and received vitamin D and calcium supplementation. He suffered a recurrence of infection with Mycobacterium avium intracellulare for which he received treatment with ciprofloxacin, rifabutin, and ethambutol. Subsequently, he developed worsening vitamin D deficiency with hypocalcaemia, secondary hyperparathyroidism and elevated markers of bone turnover culminating in an osteomalacic vertebral fracture. Correction of the vitamin D deficiency required 100,000 IU of cholecalciferol monthly. Rifabutin is a cytochrome P450 inducer, and vitamin D and its metabolites are catabolised by cytochrome P450 enzymes. We therefore propose that treatment with rifabutin led to the induction of cytochrome P450 enzymes catabolising vitamin D, thereby causing vitamin D deficiency and osteomalacia. This process might be mediated through the steroid and xenobiotic receptor (SXR).


CONCLUSIONS
Treatment with rifabutin induces the cytochrome P450 enzymes that metabolise vitamin D and patients treated with rifabutin might be at increased risk of vitamin D deficiency. In complex medication regimens involving agents that induce or inhibit cytochrome P450 enzmyes, consultation with a clinical pharmacist or pharmacologist may be helpful in predicting and/or preventing potentially harmful interactions.
Bolland
Mark J
MJ
Department of Medicine, University of Auckland, Private Bag 92 019, Auckland 1020, New Zealand. m.bolland@auckland.ac.nz
Grey
Andrew
A
Horne
Anne M
AM
Thomas
Mark G
MG
D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy; D000469:Alkaline Phosphatase / Q000032:analysis; D000900:Anti-Bacterial Agents / Q000009:adverse effects* / Q000378:metabolism / Q000627:therapeutic use; D015519:Bone Density; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000209:etiology; D008297:Male; D008875:Middle Aged; D015270:Mycobacterium avium-intracellulare Infection / Q000175:diagnosis / Q000188:drug therapy*; D010018:Osteomalacia / Q000139:chemically induced / Q000188:drug therapy / Q000209:etiology*; D017828:Rifabutin / Q000009:adverse effects* / Q000378:metabolism / Q000627:therapeutic use; D014808:Vitamin D Deficiency / Q000139:chemically induced / Q000188:drug therapy / Q000209:etiology
D000900:Anti-Bacterial Agents; D017828:Rifabutin; D003577:Cytochrome P-450 Enzyme System; D000469:Alkaline Phosphatase