Summary
Variation in the systemic disposition of theophylline after ingestion of a new microcrystalline product (Theolair®) has been investigated in 7 hospitalized patients with generalized obstructive lung disease. Disposition (absolute bioavailability) was determined by comparing in the same patients the areas under the serum concentration-time curves after a single oral dose of microcrystalline theophylline and after an intravenous infusion of aminophylline. Oral absorption appeared to be fast. The half-life of absorption was 19±9 min (mean±SD). Maximal serum concentrations reached after 100±30 min were found to be in a rather narrow range: 9.8±2.5 mg · 1−1. The absolute bioavailability of the microcrystalline preparation was high and it showed only small variation: 102.7±10.2% of the dose. Relevant pharmacokinetic parameters (half-life of elimination, volume of distribution and total body clearance) were determined after both routes of administration. Individual dosage regimens required to obtain a therapeutic serum concentration were calculated for each individual patient on the basis of the observed pharmacokinetic parameters.
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References
Berg WC, Jonkman JHG, De Vries K, Orie NGM (1979) A multidose comparative study of microcrystalline theophylline and a choline theophyllinate. Curr Med Res Opin, Suppl 6: 64–70
Cohen A, Johnson C, Osvaldo R (1975) A rapid dissolving theophylline tablet. Curr Ther Res 17: 497–505
De Blaey CJ, Rutten-Kingma JJ (1977) Biopharmaceutics of aminophylline suppositories II, In Vitro release rate during storage. Pharm Acta Helv 52: 11–14
Elwood RK, Kelly JG, McDevitt DG (1978) Pharmacokinetics of a microcrystalline theophylline preparation in patients with chronic obstructive airways disease. Eur J Clin Pharmacol 13: 29–33
Graham G, Hartnett BS, Hayter R (1974) Rapidly dissolving tablets of theophylline. Aust J Pharm Sci 13: 66–68
Hartnett BJS, Marlin GE, Graham G (1974) Clinical trial of rapidly dissolving theophylline tablets. Med J Aust 1: 532–535
Hendeles L, Bighley L, Richardson RH, Hepler CD, Carmichael J (1977) Frequent toxicity from I. V. aminophylline infusions in critically ill patients. Drug Intell Clin Pharm 11: 12–18
Hendeles L, Weinberger M, Bighley L (1978) Disposition of theophylline after a single intravenous infusion of aminophylline. Am Rev Respir Dis 118: 97–103
Holley RA, Mildon CA, French IW (1978) Single- and multi-dose bioavailability study of a new rapidly dissolving theophylline tablet. Curr Ther Res 23: 330–344
Hunt SN, Jusko WJ, Yurchak AM (1976) Effect of smoking on theophylline disposition. Clin Pharmacol Ther 19: 546–551
Jacobs MH, Senior RM, Kessler G (1976) Clinical experience with theophylline: relationship between dosage, serum concentration and toxicity. J Am Med Assoc 235: 1983–1986
Jenne JW, Wyze E, Rood FS, MacDonald FM (1972) Pharmacokinetics of theophylline: application to adjustment of the clinical dose of aminophylline. Clin Pharmacol Ther 13: 349–360
Jenne J, Nagasawa H, McHugh R, MacDonald F, Wyse E (1975) Decreased theophylline half-life in cigarette smokers. Life Sci 17: 195–197
Jonkman JHG, Schoenmaker R, Greving JE, De Zeeuw RA (1980) Rapid and selective theophylline serum and saliva assay by means of high pressure liquid chromatography. Pharm Weekbl Sci Ed 2: 49–53
Levy G, Koysooko R (1975) Pharmacokinetic analysis of the effect of theophylline on pulmonary function in asthmatic children. J Ped 86: 789–793
Lillehei JP (1968) Aminophylline oral v. s. rectal administrations. J Am Med Assoc 205: 530–533
Mitenko PA, Ogilvie RI (1973) Rational intravenous doses of theophylline. N Engl J Med 289: 600–603
Piafsky KM, Ogilvie RI (1975) Dosage of theophylline in bronchial asthma. N Engl J Med 292: 1218–1222
Powell JR, Thiercelin J-F, Vozeh S, Sansom L, Reigelman S (1977) The influence of cigarette smoking and sex on theophylline disposition. Am Rev Respir Dis 116: 17–23
Powell JR, Vozeh S, Hopewell P, Costello J, Sheiner LB, Riegelman S (1978) Theophylline disposition in acutely ill hospitalized patients; the effect of smoking, heart failure, severe airway obstruction and pneumonia. Am Rev Respir Dis 118: 229–238
Ritschel WA (1976) Handbook of Basic Pharmacokinetics. Drug Inteligence-Publications, Hamilton
Sheiner LB, Tozer TN (1978) Clinical Pharmacokinetics: the use of plasma concentrations of drugs. In: Melmon KL, Morelli HF (eds) Clinical pharmacology. MacMillan, New York
Turner-Warwick M (1957) Study of theophylline plasma levels after oral administration of new theophylline compounds. Br Med J 2: 67–69
Weinberger MW, Reigelman S (1974) Rational use of theophylline for bronchodilation. N Engl J Med 291: 151–153
Weinberger MW, Matthay RA, Ginchansky EJ, Chidsey CA, Petty TL (1976) Intravenous aminophylline dosage: use of serum theophylline measurement for guidance. J Am Med Assoc 235: 2110–2113
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Jonkman, J.H.G., Berg, W.C., Schoenmaker, R. et al. Disposition and clinical pharmacokinetics of microcrystalline theophylline. Eur J Clin Pharmacol 17, 379–384 (1980). https://doi.org/10.1007/BF00558452
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DOI: https://doi.org/10.1007/BF00558452