Summary
Results of previous studies suggest that the theophylline-verapamil drug interaction may be dependent on verapamil dose. Therefore, in a randomized four-way cross over study, 12 healthy males received theophylline, as a single intravenous dose of aminophylline, alone (phase I) and after a four day regimen of oral verapamil 40 mg (phase II), 80 mg (phase III), and 120 mg (phase IV) every 8 h. Serial blood samples were collected over a 24 hour period for determination of serum theophylline concentration and subsequent pharmacokinetic analysis.
Mean theophylline AUC for phase I–IV was 93.6, 105.6, 110.8, 120.1 mg · h · l−1, respectively. Mean theophylline clearance for phase I–IV was 3.89, 3.59, 3.35, and 3.20 l · h−1, respectively. The changes in AUC, clearance, andλ z were linearly correlated to verapamil dose.
These results suggest that the inhibitory effect of verapamil on the pharmacokinetic disposition of theophylline is directly related to verapamil dose.
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References
Rodheffer RJ, Rommer JA, Wigley F, Smith CR (1983) Controlled double-blind trial of nifedipine in the treatment of Raynaud's phenomenon. N Engl J Med 308: 880–883
Kirkegaard P, Christiansen J, Peterson B, Slov Olson P (1982) Calcium and stimulus-secretion coupling in gastric fundic mucosa. Scand J Gastroenterol 17: 533–538
Castell DO (1985) Calcium-channel blocking agents for gastrointestinal disorders. Am J Cardiol 55: 210B-213B
Massey KL, Hendeles L (1987) Calcium antagonists in the management of asthma: breakthrough or ballyhoo? Drug Intell Clin Pharm 21: 505–509
Renton KW (1985) Inhibition of hepatic microsomal drug metabolism by the calcium channel blockers diltiazem and verapamil. Biochem Pharmacol 34: 2549–2554
Bauer LA, Stenwall M, Horn JR, Davis R, Ophein K, Greene L (1986) Changes in antipyrine and indocyanine green kinetics during nifedipine, verapamil and diltiazem therapy. Clin Pharmacol Ther 40:239–242
Sirmans SM, Pieper JA, Lalonde RL, Smith D, Self TH (1988) Effect of calcium channel blockers on theophylline disposition. Clin Pharmacol Ther 44: 29–34
Abernethy DR, Egan JM, Dickinson TH, Carrum G (1988) Substrate-selective inhibition by verapamil and diltiazem: differential disposition of antipyrine and theophylline in humans. J Pharmacol Exp Ther 244: 994–999
Gin A, Stringer KA, Welage LA, Matthews GE (1989) The effect of verapamil on the pharmacokinetic disposition of theophylline in cigarette smokers. J Clin Pharmacol 29: 728–732
Robson RA, Miners JO, Birkett DJ (1988) Selective inhibitory effects of nifedipine and verapamil on oxidative metabolism: Effects of theophylline. Br J Clin Pharmacol 25: 397–400
Gibaldi M, Perrier D (1982) Noncompartmental analysis based on statistical moment theory. In: Gibaldi M, Perrier D. Pharmacokinetics. Marcel Dekker, New York, pp 409–412
Burnakis TG, Seldon M, Czaplicki AD (1983) Increased serum theophylline concentrations secondary to oral verapamil. Clin Pharm 2: 458–461
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This study was supported in part by Public Health Services, Research Grant 5 M01 RR0051 from the Division of Research Resources, The American Association of Colleges of Pharmacy, and The Upjohn Company
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Stringer, K.A., Mallet, J., Clarke, M. et al. The effect of three different oral doses of verapamil on the disposition of theophylline. Eur J Clin Pharmacol 43, 35–38 (1992). https://doi.org/10.1007/BF02280751
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DOI: https://doi.org/10.1007/BF02280751