Jonkman J H, Berg W C, de Vries K, de Zeeuw R A, Schoenmaker R, Grimberg N
Eur J Clin Pharmacol. 1981;21(1):39-44. doi: 10.1007/BF00609586.
The systemic disposition of theophylline after taking a new, sustained release tablet (Theolair Retard 250 mg, Theolair S.R., Riker Laboratories) has been studied in 8 hospitalized patients. Absolute bioavailability was determined from the ratios of the areas under the serum concentration-time curves after intake of the tablet and after intravenous infusion of aminophylline in the same patient. The absolute bioavailability of Theolair Retard 250 mg was 110.9 +/- 20.8% (mean +/-SD). Maximal serum concentrations were reached after 7.3 +/- 3.5 h, the large intersubject variation being due to differences in gastric emptying time. The tablets appear to release theophylline slowly in acid conditions, but more rapidly in an alkaline medium. Invasion was found to be either monophasic with a rate constant of about 0.8 h-1 (intestine), or biphasic with rate constants of 0.2 h-1 (stomach) and 0.8 h-1 (intestine). The peak levels accounted for 7.9 +/- 2.2 mg . 1-1. The profiles of the serum concentration-time curves were such that the concentrations remained above 80% of cmax for 6.5 +/- 3.3 h. The relevant pharmacokinetic parameters (half-life of elimination, total body clearance and volume of distribution) were determined and were used to calculate the individual dosage regimens required to obtain therapeutic serum concentrations. The optimal dosing interval to obtain an average steady state serum concentration of 12.5 mg . l-1 was 9.8 +/- 3.1 h.
在8名住院患者中研究了服用新型缓释片（Theolair Retard 250 mg，Theolair S.R.，莱克实验室）后茶碱的全身处置情况。通过同一患者服用该片剂后与静脉输注氨茶碱后血清浓度-时间曲线下面积之比来确定绝对生物利用度。Theolair Retard 250 mg的绝对生物利用度为110.9±20.8%（平均值±标准差）。最大血清浓度在7.3±3.5小时后达到，个体间差异较大是由于胃排空时间不同。该片剂在酸性条件下似乎缓慢释放茶碱，但在碱性介质中释放更快。发现吸收呈单相，肠道的速率常数约为0.8 h⁻¹，或呈双相，胃的速率常数为0.2 h⁻¹，肠道的速率常数为0.8 h⁻¹。峰值水平为7.9±2.2 mg·L⁻¹。血清浓度-时间曲线的特征是浓度在6.5±3.3小时内保持在cmax的80%以上。测定了相关的药代动力学参数（消除半衰期、全身清除率和分布容积），并用于计算获得治疗性血清浓度所需的个体给药方案。为使平均稳态血清浓度达到12.5 mg·L⁻¹的最佳给药间隔为9.8±3.1小时。
