临床药理学与生物药剂学

抽象的

Preparation of Extended-Release Theophylline for Gastric Tube Administration Significantly Impairs Gradual Resorption

Papiež Adriana, Šrámek Vladimír, Pešáková Edita, Matiňáková Libuše and Suk Pavel

Background: Although Extended Release (ER) dosage forms are not suitable for administration via Nasogastric Tube (NGT), they are used in critically ill patients. The aim of this study is to compare pharmacokinetics of intact and crushed ER theophylline capsules and tablets.

Methods: Open-label, randomized controlled trial with two parallel groups was conducted on 10 healthy volunteers. They were randomized into Theo plus^® 300 (ER tablets) and Eupyllin CR N^® 300 (capsules with ER pellets) group. Each group took the same drug orally twice-first prepared (for the NGT administration) by crushing and secondly as an intact dosage form. Theophylline serum levels were taken at baseline, 30 min, 60 min, 2 h, 4 h, 6 h, 9 h and 12 h after drug administration. _maximum serum concentration (C_max), time to reach C_max (T_max) and area under the serum concentration-time curves over 12 h (AUC12h) were calculated. Data are presented as mean ± SD.

Results: Crushing increased C_max in both Euphyllin (43.8 ± 6.5 vs. 26.5 ± 1.6 μmol/l; p<0.01) and Theoplus (45.2 ± 3.6 vs. 29.4 ± 4.8 μmol/l; p=0.013) groups. T_max was significantly shorter after administration of crushed dosage forms in Euphyllin (0.9 ± 0.7 vs. 5.6 ± 0.9 h; p<0.001) and Theoplus (1.1 ± 0.5 vs. 9.6 ± 2.5 h; p<0.01) group. Concordantly, drug crushing augmented AUC12 h by 40% in both drugs.

Conclusion: Crushing destroyed ER properties of theophylline tablets and capsules and their pharmacokinetic profiles were comparable with immediate release forms.