Grapefruit juice (GFJ) inhibits intestinal CYP3A4 activity and it has been suggested that GFJ may also inhibit renal 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2), which converts cortisol to cortisone. This study examined the effect of GFJ on the urinary excretion of cortisol, cortisone and 6β-hydroxycortisol (6β- OHC) and their ratios to asses these effects. Healthy male Chinese subjects took single doses of GFJ (200,
400, and 600 mL, respectively) at weekly intervals. Urine was collected over 24 h the day before and fol- lowing GFJ intake. Subsequently, volunteers drank 400 mL GFJ for 7 days and urine was collected from
0 to 4 h daily. GFJ had dose-dependent effects on increasing cortisol excretion (P < 0.05) and the ratio of cortisol to cortisone (P < 0.005) and reducing 6β-OHC excretion (P < 0.05) and the ratio of 6β-OHC to cor- tisol (P < 0.005). There was no significant effect on cortisone excretion. Maximal effects were observed within 4 h after GFJ ingestion. Repeated doses had persistent but no cumulative effects. GFJ signifi- cantly reduced the ratio of 6β-OHC to cortisol. It increased the ratio of cortisol to cortisone and this appeared largely due to increased cortisol excretion related to impaired CYP3A4-mediated cortisol metabolism al- though a true inhibitory effect on 11β-HSD2 in the kidney cannot be excluded.
© 2014 Elsevier Ltd. All rights reserved.
Grapefruit juice (GFJ) inhibits intestinal CYP3A4 activity and it has been suggested that GFJ may also inhibit renal 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2), which converts cortisol to cortisone. This study examined the effect of GFJ on the urinary excretion of cortisol, cortisone and 6β-hydroxycortisol (6β- OHC) and their ratios to asses these effects. Healthy male Chinese subjects took single doses of GFJ (200,
400, and 600 mL, respectively) at weekly intervals. Urine was collected over 24 h the day before and fol- lowing GFJ intake. Subsequently, volunteers drank 400 mL GFJ for 7 days and urine was collected from
0 to 4 h daily. GFJ had dose-dependent effects on increasing cortisol excretion (P < 0.05) and the ratio of cortisol to cortisone (P < 0.005) and reducing 6β-OHC excretion (P < 0.05) and the ratio of 6β-OHC to cor- tisol (P < 0.005). There was no significant effect on cortisone excretion. Maximal effects were observed within 4 h after GFJ ingestion. Repeated doses had persistent but no cumulative effects. GFJ signifi- cantly reduced the ratio of 6β-OHC to cortisol. It increased the ratio of cortisol to cortisone and this appeared largely due to increased cortisol excretion related to impaired CYP3A4-mediated cortisol metabolism al- though a true inhibitory effect on 11β-HSD2 in the kidney cannot be excluded.
© 2014 Elsevier Ltd. All rights reserved.
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Grapefruit juice (GFJ) inhibits intestinal CYP3A4 activity and it has been suggested that GFJ may also inhibit renal 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2), which converts cortisol to cortisone. This study examined the effect of GFJ on the urinary excretion of cortisol, cortisone and 6β-hydroxycortisol (6β- OHC) and their ratios to asses these effects. Healthy male Chinese subjects took single doses of GFJ (200,
400, and 600 mL, respectively) at weekly intervals. Urine was collected over 24 h the day before and fol- lowing GFJ intake. Subsequently, volunteers drank 400 mL GFJ for 7 days and urine was collected from
0 to 4 h daily. GFJ had dose-dependent effects on increasing cortisol excretion (P < 0.05) and the ratio of cortisol to cortisone (P < 0.005) and reducing 6β-OHC excretion (P < 0.05) and the ratio of 6β-OHC to cor- tisol (P < 0.005). There was no significant effect on cortisone excretion. Maximal effects were observed within 4 h after GFJ ingestion. Repeated doses had persistent but no cumulative effects. GFJ signifi- cantly reduced the ratio of 6β-OHC to cortisol. It increased the ratio of cortisol to cortisone and this appeared largely due to increased cortisol excretion related to impaired CYP3A4-mediated cortisol metabolism al- though a true inhibitory effect on 11β-HSD2 in the kidney cannot be excluded.
© 2014 Elsevier Ltd. All rights reserved.
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