Unexpected drug-drug interactions in human immunodeficiency virus (HIV) therapy: induction of UGT1A1 and bile efflux transporters by Efavirenz
Annals of the Academy of Medicine, Singapore
;
: 559-562, 2012.
Artículo
en Inglés
| WPRIM
| ID: wpr-299585
ABSTRACT
<p><b>INTRODUCTION</b>Efavirenz is an inducer of drug metabolism enzymes. We studied the effect of efavirenz and ritonavir-boosted darunavir on serum unconjugated and conjugated bilirubin, as probes for UGT1A1 and bile transporters.</p><p><b>MATERIALS AND METHODS</b>Healthy volunteers were enrolled in a clinical trial. There were 3 periods Period 1, 10 days of darunavir 900 mg with ritonavir 100 mg once daily; Period 2, 14 days of efavirenz 600 mg with darunavir/ritonavir once daily; and Period 3, 14 days of efavirenz 600 mg once daily. Serum bilirubin (conjugated and unconjugated) concentrations were obtained at baseline, at the end of each phase and at exit.</p><p><b>RESULTS</b>We recruited 7 males and 5 females. One subject developed grade 3 hepatitis on efavirenz and was excluded. Mean serum unconjugated bilirubin concentrations were 6.09 μmol/L (95% confidence interval [CI], 4.99 to 7.19) at baseline, 5.82 (95% CI, 4.88 to 6.76) after darunavir/ritonavir, 4.00 (95% CI, 2.92 to 5.08) after darunavir/ritonavir with efavirenz, 3.55 (95% CI, 2.58 to 4.51) after efavirenz alone and 5.27 (95% CI, 3.10 to 7.44) at exit (P <0.01 for the efavirenz phases). Mean serum conjugated bilirubin concentrations were 3.55 μmol/L (95% CI, 2.73 to 4.36) at baseline, 3.73 (95% CI, 2.77 to 4.68) after darunavir/ritonavir, 2.91 (95% CI, 2.04 to 3.78) after darunavir/ritonavir with efavirenz, 2.64 (95% CI, 1.95 to 3.33) after efavirenz alone and 3.55 (95% CI, 2.19 to 4.90) at exit (P <0.05 for the efavirenz phases).</p><p><b>CONCLUSION</b>Efavirenz decreased unconjugated bilirubin by 42%, suggesting UGT1A1 induction. Efavirenz also decreased conjugated bilirubin by 26%, suggesting induction of bile efflux transporters. Ritonavir-boosted darunavir had no effect on bilirubin concentrations. These results indicate that efavirenz may reduce concentrations of drugs or endogenous substances metabolized by UGT1A1 or excreted by bile efflux transporters.</p>
Texto completo:
Disponible
Índice:
WPRIM (Pacífico Occidental)
Asunto principal:
Proteínas de Transporte de Membrana
/
Farmacología
/
Sulfonamidas
/
Transporte Biológico
/
Sangre
/
Intervalos de Confianza
/
Infecciones por VIH
/
Inducción Enzimática
/
Glucuronosiltransferasa
/
Inhibidores de la Proteasa del VIH
Tipo de estudio:
Estudio diagnóstico
Límite:
Adulto
/
Anciano
/
Femenino
/
Humanos
/
Masculino
Idioma:
Inglés
Revista:
Annals of the Academy of Medicine, Singapore
Año:
2012
Tipo del documento:
Artículo
Similares
MEDLINE
...
LILACS
LIS