Summary
In a double blind, placebo controlled, crossover study the pharmacokinetics and acute effects of enprofylline and theophylline on airway reactivity during histamine challenge were investigated in 10 healthy volunteers. The pharmacokinetic parameters of enprofylline were (mean): elimination half-life 1.9 h, total body clearance 191.1 ml · kg−1 · h−1, volume of distribution 0.48 l · kg−1, and protein binding 49%. Bronchial reactivity in the histamine inhalation test was expressed as the concentration causing a 20% fall in FEV1.0 (PC20). Mean PC20 values were lowest after placebo and highest after theophylline with the enprofylline values in between. Only the difference in PC20 Safter placebo and theophylline was statistically significant (p<0.05). At the time of determination of the PC20, the serum concentration of enprofylline was between 16.5 and 11.8 µmol/l, and that of theophylline was between 78.3 and 61.1 µmol/l. Adverse actions of enprofylline were nausea (3/10) and cardiovascular reactions (2/10), whereas theophylline mainly caused restlessness (3/10) and tremor (2/10). Thus enprofylline, in one-fifth of the serum concentration of theophylline cannot be regarded as equipotent in terms of bronchoprotection.
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Persson CGA, Kjellin G (1981) Enprofylline, a principally new antiasthmatic xanthine. Acta Pharmacol Toxicol 49: 313–316
Lunell E, Svedmyr N, Andersson K-E, Persson CGA (1982) Effects of enprofylline, a xanthine lacking adenosine receptor antagonism, in patients with chronic obstructive lung disease. Eur J Clin Pharmacol 22: 395–402
Laursen IC, Johannesson N, Weeke B (1984) Continuous treatment of asthmatic patients with enprofylline and theophylline. Eur J Respir Dis 65: 504–508
Lunell E, Anderssen KE, Persson CGA (1983a) Tolerance and some circulatory effects of intravenous and oral enprofylline in healthy volunteers. Acta Pharmacol Toxicol 53: 205–211
Hargreave FE, Thompson NC, O'Byrne PM, Latimer K, Juniper EF, Dolowich J (1981) Bronchial responsiveness to histamine or metacholine in asthma: Measurement and clinical significance. J Allergy Clin Immunol 68: 347–355
Cockcroft DW, Killian DN, Mellon JJA, Hargreave FE (1977) Bronchial reactivity to inhaled histamine: A method and clinical survey. Clin Allergy 7: 235–243
Lunell E, Borgå O, Larsson R (1984b) Pharmacokinetics of enprofylline in asthma patients. Eur J Clin Pharmacol 26: 87–93
Oellerich M, Müller-Vahl H (1984) The EMIT Free Level IM ultrafiltration technique compared with equilibrium dialysis and ultracentrifugation to determine protein binding of phenytoin. Clin Pharmacokinet 9 [Suppl 1]: 61–70
Borgå O, Andersson KE, Edholm LE, Fagerstrom PO, Lunell E, Persson CG (1983) Enprofylline kinetics in healthy subjects after single doses. Clin Pharmacol Ther 34: 799–804
Salter H (1859) On some points in the treatment and clinical history of asthma. Edinb Med J: 1109–1115
Becker AB, Simons KJ, Gillespie CA, Simons FE (1984) The bronchodilator effects and pharmacokinetics of caffeine in asthma. N Engl J Med 310: 743–746
Lunell E, Andersson KE, Persson CGA, Svedmyr N (1984a) Intravenous enprofylline in asthma patients. Eur J Respir Dis 65: 28–34
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In fulfillment of his thesis (Dr. med.)
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Kluge, T.B.R., Oellerich, M., Schumann, G. et al. Enprofylline: Pharmacokinetics and comparison with theophylline of acute effects on bronchial reactivity in normal subjects. Eur J Clin Pharmacol 30, 21–25 (1986). https://doi.org/10.1007/BF00614190
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DOI: https://doi.org/10.1007/BF00614190