Biotransformation of tirilazad in human: 2. Effect of ketoconazole on tirilazad clearance and oral bioavailability

Journal of Pharmacology and Experimental Therapeutics

Volumn 277, Issue 2, 1996, Pages 991-998

  Fleishaker, Joseph C ^a   Pearson, Paul G ^a   Wienkers, Larry C ^a   Pearson, Laura K ^a   Peters, Gary R ^a  

^a PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DRUG METABOLITE; KETOCONAZOLE; TIRILAZAD;

ARTICLE; BRAIN INJURY; CLINICAL ARTICLE; CLINICAL TRIAL; CROSSOVER PROCEDURE; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG TRANSFORMATION; ENZYME ACTIVITY; HUMAN; INTRAVENOUS DRUG ADMINISTRATION; LIPID PEROXIDATION; LIVER MICROSOME; ORAL DRUG ADMINISTRATION; PRIORITY JOURNAL; SUBARACHNOID HEMORRHAGE;

ADULT; ANTIOXIDANTS; BIOLOGICAL AVAILABILITY; BIOTRANSFORMATION; CROSS-OVER STUDIES; CYTOCHROME P-450 ENZYME SYSTEM; ENZYME INHIBITORS; FEMALE; HUMANS; KETOCONAZOLE; MALE; METABOLIC CLEARANCE RATE; MIDDLE AGED; PREGNATRIENES;

EID: 0030430049     PISSN: 00223565     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (27)

1. BAILEY, D. G., ARNOLD, J. M. O. AND SPENCE, J. D.: Grapefruit juice and drugs: How significant is the interaction. Clin. Pharmacokinet. 26: 91-98, 1994.
2. BLECK, T. B., GERMANSON, T. P., JANE, J. A. AND THE PARTICIPANTS IN THE TIRILAZAD HEAD TRAUMA TRIAL, PHASE II: Tirilazad mesylate is safe in patients with moderate or severe head trauma (abstract). Neurology 45: suppl. 4, A345, 1995.
3. BOMBARDT, P. A., BREWER, J. E. AND JOHNSON, M. G.: Protein binding of tirilazad (U-74006) in human, sprague-dawley rat, beagle dog and cynomolgous monkey serum. J. Pharmacol. Exp. Ther. 269: 145-150, 1994.
4. BRAUGHLER, J. M., HALL, E. D., JACOBSEN, J., MCCALL, J. M. AND MEANS, E. D.: The 21-aminosteroids: Potent inhibitors of lipid peroxidation for the treatment of central nervous system trauma and ischemia. Drugs Future 14: 143-152, 1989.
5. COX, J W., LARSON, P. G., WYNALDA, M. A , SOOD, V K., VERBURG, M. T. AND PULLEN, R. N.: Pharmacokinetics and excretion of the 21-aminosteroid antioxidant U-74006F in rat and perfused rat liver. Drug Metab. Dispos. 17: 373-379, 1989.
6. FLEISHAKER, J. C., PEARSON, L. K. AND PETERS, G. R.: Evaluation of the time course of induction of cytochrome P-450 by phenytoin in man. J. Pharm. Sci. 84: 292-294, 1995.
7. FLEISHAKER, J. C., HULST, L K. AND PETERS G. R.: Multiple dose tolerability and pharmacokinetics of tirilazad mesylate at doses of up to 10 mg/kg/day administered over 5-10 days in healthy volunteers. Int. J. Clin Pharmacol. Ther. 32: 223-230, 1994a.
8. FLEISHAKER, J. C., HULST-PEARSON, L. K. AND PETERS, G. R.: The effect of phenytoin on the pharmacokinetics of tirilazad mesylate in healthy male volunteers. Clin Pharmacol. Ther. 56: 389-397, 1994b.
9. GED, C., ROUILLON, J. M., PICHARD, L., COMBALBERT, J., BRESSOT, N., BORIES, P., MICHEL, H., BEAUNE, P. AND MAUREL, P.: The increase in urinary excretion of 6β-hydroxycortisol as a marker of human hepatic cytochrome P450IIIA induction Br. J. Clin. Pharmacol. 28: 373-387, 1989.
10. GIBALDI, M. AND PERRIER, D.: Pharmacokinetics, 2nd ed. Marcell Dekker, New York, 1982.
11. GOMEZ, D., HEBERT, M. AND BENET, L. Z.: The effect of ketoconazole on the intestinal metabolism and bioavailability of cyclosporine (abstract). Clin. Pharmacol. Ther. 55: 209, 1994.
12. HALEY, E. C., PUTMAN, S., ANDERSON, F., MORRISON, M. R., TUTTLE, P., PASSINI, B. T., WILNER A. N., ALLEN, F. H , ADAMS, R., CARL, B., BUEKE, C., NICHOLS, F., HESS, D., HYDER, S., BURCH, G., FOLEY, C., BIVINS, D. H., WILSON, J. T., SISK, M. A , NOLAN, D. B., ELIAS, W. S., SHEPPARD, G. L., CROWE, N. F., MASSEY S., HURST, D., ZONETINE, D., GUSTIN, K. H., MCCLURE, K., GRANNER, M., WOLF, S., GWYNN, M., METTETAL, R. W., TORNER, J. C., KONGABLE, G., WILKINSON, S., HANSEN, C. A., WOLFF, M. C., GIRSON, R. S., BERGIN, J D., TRUSKOWSKI, L., LIGHTFOOT, G., LIGHTFOOT, A., POLIN, A., SOLENSKI, N. J., STITELER, J., PETERS, G. R. AND BRYAN, W J.: Safety study of tirilazad mesylate in patients with acute ischemic stroke. Stroke 25: 418-423, 1994.
13. HALPERT, J. R., GUENGERICH, F. P., BEND, J. R. AND CORREIA, M. A : Contemporary issues in toxicology: Selective inhibitors of cytochromes P-450. Toxicol. Appl. Pharmacol. 125: 163-175, 1994.
14. HEBERT, M F., ROBERTS, J. P., PRUEKSARITANONT, T. AND BENET, L. Z.: Bioavailability of cyclosporine with concomitant rifampin administration is markedly less than predicted by hepatic enzyme induction. Clin. Pharmacol. Ther. 52: 453-457, 1992.
15. HOPKINS, N. K., LARSON, M. K. AND HANSON, G. D.: Determination of tirilazad mesylate (U-74,006F) and its metabolite (M-1) in human plasma using high performance liquid chromatography. Presented at the 4th International Symposium on Pharmaceutical and Biomedical Analysis, Baltimore, MD, April 1993.
16. KASSELL, N. F., HALEY, E. C., ALVES, W. M., HANSEN, C. A., WEIR, B. AND THE PARTICIPANTS: Phase two trial of tirilazad in aneurysmal subarachnoid hemorrhage (abstract). Can. J. Neurol. Sci., 20: suppl. 1, S29, 1993.
17. KASSELL, N. F., HALEY, E. C., APPERSON-HANSEN, C., ALVES, W. M. AND THE PARTICIPANTS: A randomized, double-blind, vehicle-controlled trial of tirilazad mesylate in patients with aneurysmal subarachnoid hemorrhage: A cooperative study in Europe/Australia/New Zealand. J. Neurosurg. 1996;84: 221-228.
18. KINIRONS, M. T., O'SHEA, D., DOWNING, T. E., FITZWILLIAM, A. T., JOELLENBECK, L., GROOPMAN, J. D., WILKINSON, G. R. AND WOOD, A. J. J.: Absence of correlations among three putative probes of human cytochrome P4503A activity in young healthy men. Clin Pharmacol. Ther. 54: 621-629, 1993.
19. KRISHNA, D. R. AND KLOTZ, U.: Extrahepatic metabolism of drugs in humans. Clin. Pharmacokinet. 26: 144-160, 1994.
20. LOWN, K. S., KOLARS, J. C., THUMMEL, K. E., BARNETT, J. L., KUNZE, K. L., WRIGHTON, S. A. AND WATKINS, P. B.: Interpatient heterogeneity in expression of CYP3A4 and CYP3A5 in small bowel: Lack of prediction by erythromycin breath test. Drug Metab. Dispos. 22: 947-955, 1994.
21. OHNHAUS, E. E., BRECKENRIDGE, A. M. AND PARK, B. K.: Urinary excretion of 6β-hydroxycortisol and the time course measurement of enzyme induction in man. Eur. J. Clin. Pharmacol. 36: 39-46, 1989.
22. PASCUCCI, V. L., BENNETT, J., NARANG, P. K. AND CHATTERJI, D. C.: Quantitation of ketoconazole in biological fluids using high performance liquid chromatography. J. Pharm. Sci. 72: 1467-1469, 1983.
23. SMITH, S. L., SCHERCH, H. M. AND HALL, E. D.: Protective effects of tirilazad mesylate and metabolite U-89678 against blood-brain barrier damage after subarachnoid hemorrhage and lipid peroridative neuronal injury. J. Neurosurg., in press.
24. STRYD, R. P., WYNALDA, M. A., VERBURG, M. T., RYKERT, U. M., SHAH, J. A., FLEISHAKER, J C. AND KAISER, D. G.: Comparison of intact drug vs. total drug-related materials in plasma following single-dose IV administration of (14C)tirilazad mesylate to rabbit, dog, monkey and human (abstract). Pharm. Res. 9: suppl., S312 , 1992.
25. 4-5α-reductase. Drug Metab. Dispos. 23: 383-392, 1995.
26. WIENKERS, L. C., STEENWYK, R. C., SANDERS, P. E. AND PEARSON, P. G.: Biotransformation of Tirilazad in Human: 1. Cytochrome P450 3A-mediated hydroxylation of Tirilazad mesylate in human liver microsomes. J. Pharmacol. Exp. Ther. 277: 000-000, 1996.
27. WILKINSON, G. R. AND SHAND, D. G.: A physiological approach to hepatic drug clearance. Clin. Pharmacol. Ther. 18: 377-390, 1975.