Ramsay L E, Mackay A, Eppel M L, Oliver J S
Br J Clin Pharmacol. 1980 Aug;10(2):101-7. doi: 10.1111/j.1365-2125.1980.tb01725.x.
1 Consecutive medical inpatients expected to benefit from a theophyllinate were treated with sustained-release aminophylline in a protocol conforming with ordinary practice. Of 16 patients, five had toxicity with aminophylline 450 mg daily, and a further three with 900 mg daily. Toxicity was serious in three patients. 2 Toxicity was significantly less common in cigarette smokers, and was related to higher plasma theophylline concentrations. However, there was a large overlap between concentrations associated with toxicity (as low as 9 micrograms/ml) and the accepted therapeutic range (5-20 micrograms/ml). Most patients with toxicity had theophylline levels within the therapeutic range. 3 For the same dose of aminophylline there was sevenfold variation between patients in plasma theophylline, with higher concentrations in non-smokers, infrequent alcohol users, older patients, those with left ventricular failure and those with lower serum transaminases. There variables could not be separated completely because of the small number of observations. 4 A nomogram for aminophylline dosage or monitoring of serum theophylline levels would have prevented little of the toxicity observed in these patients, although these measures would ensure that therapeutic concentrations were attained, and might prevent life-threatening toxicity.
预计能从茶碱盐中获益的连续住院患者，按照常规做法接受缓释氨茶碱治疗。16例患者中，5例在每日服用450毫克氨茶碱时出现毒性反应，另有3例在每日服用900毫克时出现毒性反应。3例患者的毒性反应较为严重。
毒性反应在吸烟者中明显较少见，且与较高的血浆茶碱浓度有关。然而，与毒性反应相关的浓度（低至9微克/毫升）和公认的治疗范围（5 - 20微克/毫升）之间有很大重叠。大多数出现毒性反应的患者，其茶碱水平在治疗范围内。
对于相同剂量的氨茶碱，患者之间的血浆茶碱浓度存在7倍的差异，非吸烟者、不常饮酒者、老年患者、左心室衰竭患者以及血清转氨酶较低的患者，其血浆茶碱浓度较高。由于观察数量较少，这些变量无法完全区分开来。
尽管氨茶碱剂量图表或监测血清茶碱水平的措施能够确保达到治疗浓度，并可能预防危及生命的毒性反应，但对于预防这些患者中观察到的毒性反应作用不大。
