Summary
The plasma pharmacokinetics of nifedipine and the formation of its metabolites have been studied in volunteers under conditions which would affect the activity of the cytochrome P-450 system.
The pharmacokinetics of a 10-mg capsule of nifedipine were not significantly different between smokers and non-smokers of similar age.
After pretreatment with cimetidine, which inhibits the activity of cytochrome P-450, the peak plasma concentration and area under the plasma-time concentration curve for nifedipine were increased by a mean 84%. In contrast, pre-treatment with ranitidine which has little effect on cytochrome P-450, did not significantly alter nifedipine pharmacokinetics.
Smoking does not contribute significantly to the variability in nifedipine pharmacokinetics. However, the interaction between nifedipine and cimetidine, but not ranitidine, may be of clinical importance.
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References
Baarnhielm C, Skanberg I, Borg KO (1984) Cytochrome P-450-dependent oxidation of felodipine — a 1,4-dihydropyridine — to the corresponding pyridine. Xenobiotica 14: 719–726
Baarnhielm C, Hansson G (1986) Oxidation of 1-4-dihydropyridines by prostaglandin synthase and the peroxidic function of cytochrome P-450. Biochem Pharmacol 35: 1419–1425
Banzet O, Colin JN, Thibonnier M, Singlas E, Alexandre JM, Corvol P (1983) Acute anti-hypertensive effect and pharmacokinetics of a tablet preparation of nifedipine. Eur J Clin Pharmacol 24: 145–150
Bell JA, Gower AJ, Martin LE, Mills ENC, Smith WP (1981) Interaction of H2-receptor antagonists with drug-metabolising enzymes. Biochem Soc Trans 9: 113–114
Breen KJ, Bury R, Desmond PV, Mashford ML, Morphett B, Westwood B, Shaw RG (1982) Effects of cimetidine and ranitidine on hepatic drug metabolism. Clin Pharmacol Ther 31: 297–300
Challenor VF, Waller DG, Gruchy BS, Renwick AG, George CF (1987) Food and nifedipine pharmacokinetics. Br J Clin Pharmacol 23: 248–249
Conney AH (1967) Pharmacological implications of microsomal enzyme induction. Pharmacol Rev 19: 317–366
Deanfield J, Wright C, Krikler S, Ribiero P, Fox K (1984) Cigarette smoking and the treatment of angina with propranolol, atenolol and nifedipine. New Engl J Med 310: 951–954
Feely J, Guy E (1982) Ranitidine also reduces liver blood flow. Lancet 1: 169
Feely J, Wilkinson GR, Wood AJJ (1981) Reduction of liver blood flow and propranolol metabolism by cimetidine. N Engl J Med 304: 692–695
Foster TS, Hamann SR, Richards VR, Bryant PJ, Graves DA, McAllister RG (1983) Nifedipine kinetics and bioavailability after a single oral dose in normal subjects. J Clin Pharmacol 23: 161–170
Gibaldi M, Perrier D (1982) Pharmacokinetics (2nd edn revised and expanded). Marcel Dekker, New York
Hamann SR, Tan TG, Kaltenborn KE, Brower KLR, Blouin RA, Chang SL, Vore M, McAllister RG (1985) Effects of phenobarbital and SKF-525A on in vitro hepatic metabolism of verapamil and nifedipine. Pharmacology 30: 121–128
Horster FA, Duhm B, Maul W, Medenwald H, Patzschke K, Wegner LA (1972) Clinical investigations on the pharmacokinetics of radioactively marked 4-(2′-nitrophenyl)-2,6-dimethyl-1,4-dihydropyridine3,5-dicarboxylic acid dimethyl ester. Arzneimittelforsch (Drug Res) 22: 330–334
Kirch W, Janisch HD, Heidemann H, Ramsch K, Ohnhaus E (1983) Einfluß von Cimetidin und Ranitidin auf Pharmacokinetik und antihypertensiven Effekt von Nifedipin. Dtsch Med Wochenschr 108: 1757–1761
Kirch W, Hoensch H, Janisch HD (1984) Interactions and non-interactions with ranitidine. Clin Pharmacokinet 9: 493–510
Kleinbloesem CH, Van Harten J, Van Brummelen P, Breiner DD (1984) Liquid chromatographic determination of nifedipine in plasma and its main metabolite in urine. J Chromatogr 308: 209–216
Miller RR (1977) Effects of smoking on drug action. Clin Pharmacol Ther 22: 749–756
Piper DW (1983) Drugs for the prevention of peptic ulcer recurrence. Drugs 26: 439–453
Raemsch KD, Sommer J (1983) Pharmacokinetics and metabolism of nifedipine. Hypertension 5: II18-II24
Rendic S, Akbic-Kolbah T, Kajfez F, Ruf HH (1982) Interaction of ranitidine with liver microsomes. Xenobiotica 12: 9–17
Rendic S, Sunjic V, Toso R, Kajfez F, Ruf HH (1979) Interaction of cimetidine with liver microsomes. Xenobiotica 9: 555–564
Somogyi A, Gugler R (1982) Drug interactions with cimetidine. Clin Pharmacokinet 7: 23–41
Thibonnier M, Bonnet F, Corvol P (1980) Antihypertensive effect of fractionated sublingual administration of nifedipine in moderate essential hypertension. Eur J Clin Pharmacol 17: 161–164
Vestal RE, Wood AJJ (1980) Influence of age and smoking on drug kinetics in man. Studies using model compounds. Clin Pharmacokinet 5: 309–319
Waller DG, Renwick AG, Gruchy BS, George CF (1984) The first pass metabolism of nifedipine in man. Br J Clin Pharmacol 18: 951–954
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renwick, A.G., Le Vie, J., Challenor, V.F. et al. Factors affecting the pharmacokinetics of nifedipine. Eur J Clin Pharmacol 32, 351–355 (1987). https://doi.org/10.1007/BF00543968
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DOI: https://doi.org/10.1007/BF00543968