Reference

Chronopharmacokinetics of theophylline after sustained release and intravenous administration to adults

Chronopharmacokinetics of theophylline after sustained release and intravenous administration to adults. Jonkman, J. H. G.; Van der Boon, W. J. V.; Balant, L. P.; Schoenmaker, R.; Holtkamp, A. (Dep. Biopharm. Clin. Pharmacokinet., Lab. Drug Anal., Assen, Neth.). Eur. J. Clin. Pharmacol., 26(2), 215-22 (English) 1984. CODEN: EJCPAS. ISSN: 0031-6970. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) The influence of time of drug administration on the pharmacokinetics was studied both after ingestion of a sustained-release tablet, contg. choline theophyllinate (Zy 15061-S.R.; Teovent; Sabidal; ZYMA S.A.) [4499-40-5] and after i.v. infusion of aminophylline [317-34-0] to healthy volunteers. Both drugs were administered in the morning (10 a.m.) and on a sep. occasion in the evening (10 p.m.) after a 12 h period of fasting. After oral administration of a dose of 540 mg theophylline, the drug was steadily absorbed, both during day-time and during night-time. In some subjects, absorption was slower in the evening. Max. theophylline plasma concns. were reached after 3.3 h and 3.9 h, resp. The max. plasma concns. were almost identical after administration in the morning and in the evening (12.6 and 13.1 mg/L, resp.). There was also no significant difference between the areas under the plasma concn.-time curves after oral and i.v. administration, both at day-time and at night-time. This finding indicates complete bioavailability of the sustained release tablets on both occasions. After administration of the tablets in the morning, the plasma concn. 12 h post dosing was significantly lower than after administration in the evening. A similar observation was done after i.v. administration of the drug. This phenomenon could be explained by the finding of a significantly prolonged half-life of theophylline during night-time, provided that the plasma concns. were in the range of 5 to 15 mg/L (which coincides approx. with the therapeutic range of the drug). For day-time elimination, the half-life of theophylline was 6.2 h and for night-time elimination 8.0 h, which means an increase of 29.6% during the night. The prolonged half-life of theophylline at night-time might be of therapeutic benefit in preventing bronchus obstruction in the morning.

Circadian variation in theophylline elimination

Circadian variation in theophylline elimination. Jonkman, J. H. G.; Balant, L. P.; Van der Boon, W. J. V.; Schoenmaker, R.; Holtkamp, A. (Lab. Drug Anal., Dep. Biopharm. Clin. Pharmacokinet., Assen 9400 AC, Neth.). Biopharm. Pharmacokinet., Eur. Congr., 2nd, Volume 1, 591-6. Edited by: Aiache, J. M.; Hirtz, J. Lavoisier: Paris, Fr. (English) 1984. CODEN: 53JFAA. DOCUMENT TYPE: Conference CA Section: 1 (Pharmacology) Section cross-reference(s): 63 In humans, ingestion of Zy 15061 [4499-40-5] (a theophylline [58-55-9] sustained-release formulation) on an empty stomach resulted in consistent absorption profiles with peaks after ~3-4 h. Absorption was slightly slower during the evening, but the amt. absorbed was not different (u100%) when given at 10 a.m. or at 10 p.m. When the plasma concns. were in the therapeutic range (about 5-15 mg/L), the rate of elimination of theophylline was reduced by ~20-30% during the evening. Thus, the plasma concns. 12 h after dosing in the evening were ~20-30% higher than those obsd. 12 h after dosing in the morning. Similar results were obsd. after the administration of theophylline as i.v. aminophylline [317-34-0]. The slightly slower elimination at night might be of clin. benefit in preventing bronchus obstruction in the morning.