Metabolism of the calcium antagonist, mibefradil (POSICOR(TM), Ro 40-5967). Part III. Comparative pharmacokinetics of mibefradil and its major metabolites in rat, marmoset, cynomolgus monkey and man

Xenobiotica

Volumn 27, Issue 6, 1997, Pages 557-571

  Wiltshire, H R ^a   Sutton, B M ^a   Heeps, G ^a   Betty, A M ^a   Angus, D W ^a   Harris, S R ^a   Worth, E ^a   Welker, H A ^b  

^a ROCHE PRODUCTS LTD   (United Kingdom)

^b F HOFFMANN LA ROCHE LTD   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

CALCIUM ANTAGONIST; DRUG METABOLITE; MIBEFRADIL;

ADULT; AGED; ANIMAL EXPERIMENT; ARTICLE; CONTROLLED STUDY; DRUG BLOOD LEVEL; DRUG HYDROLYSIS; DRUG HYDROXYLATION; DRUG IDENTIFICATION; DRUG METABOLISM; FEMALE; HUMAN; HUMAN EXPERIMENT; MALE; MARMOSET; MONKEY; NONHUMAN; ORAL DRUG ADMINISTRATION; RAT; SPECIES DIFFERENCE;

ADULT; AGED; ANIMALS; BENZIMIDAZOLES; BIOTRANSFORMATION; CALCIUM CHANNEL BLOCKERS; CALLITHRIX; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; FEMALE; HUMANS; HYDROXYLATION; MACACA FASCICULARIS; MALE; MASS SPECTROMETRY; MIBEFRADIL; MIDDLE AGED; RATS; RATS, SPRAGUE-DAWLEY; SPECIES SPECIFICITY; TETRAHYDRONAPHTHALENES;

ANIMALIA; MACACA FASCICULARIS; MARMOSETS; PRIMATES;

EID: 0031007978     PISSN: 00498254     EISSN: None     Source Type: Journal    
DOI: 10.1080/004982597240343     Document Type: Article

References (13)

1. BERNINK, J. J. L. M., PRAGER, G., SCHELLING, A. and KOBRIN, I., 1996, Antihypertensive properties of the novel calcium antagonist mibefradil (Ro 40-5967). A new generation of calcium antagonists? Hypertension, 27, 426-432.
2. CLOZEL, J-P., BANKEN, L. and OSTERRIEDER, W., 1989, Effects of Ro 40-5967, a novel calcium antagonist, on myocardial function during ischemia induced by lowering coronary perfusion pressure in dogs: comparison with verapamil. Journal of Cardiovascular Pharmacology, 14, 713-721.
3. CLOZEL, J.-P., OSTERRIEDER, W., KLEINBLOESSEM, C. H., WELKER, H. A., SCHLÄPPI, B., TUDOR, R., HEFTI, H., SCHMITT, R. and EGGERS, H., 1991, Ro 40-5967: a new non-dihydropyridine calcium antagonist. Cardiovascular Drug Reviews 9, 4-17.
4. 2+ channels by Ro 40-5967. Circulation Research 75, 144-148.
5. OPERIL S. and CALHOUN, D. A., 1991, The calcium antagonist in the 1990s: an overview. American Journal of Hypertension, 4, 396S-405S.
6. 2+ channel blocker with potent vasodilator but weak inotropic action, Journal of Cardiovascular Pharmacology 13, 754-759.
7. PORTEGIES, M. C. M., SCHMITT, R., KRAAIJ, C. J., BRAAT, S. H. J. G., GUSSNER, A., HAGERMEIJER, F., POZENEL, H., PRAGER, G., VIERSMA, J. W., VAN DER WALL, E. E., KLEINBLOESSEM, C. H. and LIE, K. E., 1991, Lack of negative inotropic effects of the new calcium antagonist Ro 40-5967 in patients with chronic stable angina pectoris. Journal of Cardiovascular Pharmacology 18, 746-751.
8. 2+ channel in cardiac tissue. European Journal of Pharmacology, 290, 155-158.
9. TRIGGLE, D. J., 1991, Sites, mechanism of action and differentiation of calcium channel antagonists. American Journal of Hypertension, 4, 422S-429S.
10. WELKER, H. A., EGGERS, H., KLEINBLOESSEM, CH., ERB, K., BREITHAUPT, K., BUTZER, R. and BELZ, G. G., 1989, Ro 40-5967: pharmacokinetics of a new calcium antagonist. European Journal of Clinical Pharmacology, 36, (suppl.), A304.
11. WILTSHIRE, H. R., HARRIS, S. R., PRIOR, K. J., KOZLOWSKI, U. M. and WORTH, E., 1992, Metabolism of calcium antagonist Ro 40-5967: a case history of the use of diode-array UV spectroscopy and thermospray-mass spectrometry in the elucidation of a complex metabolic pathway. Xenobiotica, 22, 837-857.
12. WILTSHIRE, H. R., SUTTON, B. M., HEEPS, G., BETTY, A. M., ANGUS, D. A., MADIGAN, M. J. and SHARP, S. R., 1997, The metabolism of the calcium antagonist, mibefradil (POSICOR™, Ro 40-5967). Part II, metabolism in hepatic microsomes from rat, marmoset, cynomolgus monkey, rabbit and man. Xenobiotica, 27, 539-566.
13. WOOD, A., 1989, Calcium antagonists: pharmacological differences and similarities, Circulation, 80 (suppl. IV), IV.84-88.