Identification of human cytochrome P450 isoforms that contribute to all-trans-retinoic acid 4-hydroxylation

2000 ◽  
Vol 60 (4) ◽  
pp. 517-526 ◽  
Author(s):  
Lynda C McSorley ◽  
Ann K Daly
Keyword(s):  
Cytochrome P450 ◽  
Retinoic Acid ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Human Cytochrome ◽  
Cytochrome P450 Isoforms

Effect of cytochrome P450 inhibitors (diethyl dithiocarbamate, ketoconazole and grapefruit juice) on the pharmacokinetics of all-trans-retinoic acid

Il Farmaco ◽  
2004 ◽  
Vol 59 (9) ◽  
pp. 697-702 ◽  
Author(s):  
Anas Saadeddin ◽  
Francisca Torres-Molina ◽  
Jaime Cárcel-Trullols ◽  
Amparo Araico ◽  
José Esteban Peris
Keyword(s):  
Cytochrome P450 ◽  
Retinoic Acid ◽  
Grapefruit Juice ◽  
Diethyl Dithiocarbamate ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
P450 Inhibitors

Phase I evaluation of all-trans retinoic acid with and without ketoconazole in adults with solid tumors.

1995 ◽  
Vol 13 (6) ◽  
pp. 1501-1508 ◽  
Author(s):  
J S Lee ◽  
R A Newman ◽  
S M Lippman ◽  
F V Fossella ◽  
M Calayag ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Retinoic Acid ◽  
Cytochrome P450 Enzymes ◽  
Short Term ◽  
Time Curve ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
To Receive ◽  
Randomized Crossover Study ◽  
Over Time

PURPOSE All-trans retinoic acid (RA) induces accelerated plasma all-trans RA clearance, presumably via cytochrome P450 enzymes. This accelerated metabolism has been shown to be inhibited in the short term by the cytochrome P450 inhibitor ketoconazole. This study was conducted to evaluate the efficacy of ketoconazole in maintaining plasma all-trans RA levels over time. PATIENTS AND METHODS Using a randomized crossover study design, we randomly assigned six patients to receive all-trans RA (45 mg/m2 orally twice per day for 14 days of a 21-day cycle) for cycle 1 and the same dose of all-trans RA plus ketoconazole (400 mg orally for one dose, then 200 mg orally three times per day for 14 days) for cycle 2, and seven patients to receive the same treatment in the reverse order. Plasma all-trans RA levels were measured during the initial 8-hour period after all-trans RA ingestion on days 1 and 15 of cycles 1 and 2. RESULTS There was a marked decrease in plasma all-trans RA levels after 14 days of treatment, as measured by the area under the concentration-time curve (AUC), regardless of whether ketoconazole was given (from a baseline value of 857 to 44 ng/mL/h; P = .025) or not (from 1,355 to 308 ng/mL/h; P = .123). This lack of effect on plasma all-trans RA levels was not due to inadequate plasma ketoconazole levels. Ketoconazole administration was associated with more toxicity. No objective tumor responses were observed. CONCLUSION Ketoconazole does not appear to maintain adequate plasma all-trans RA levels over time.

Identification of Human Cytochrome P450s Involved in the Formation of All-trans-Retinoic Acid Principal Metabolites

2000 ◽  
Vol 58 (6) ◽  
pp. 1341-1348 ◽  
Author(s):  
Julie Marill ◽  
Thierry Cresteil ◽  
Michel Lanotte ◽  
Guy G. Chabot
Keyword(s):  
Retinoic Acid ◽  
Cytochrome P450s ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Human Cytochrome
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