Watling S, Engelhardt J, Kandrotas R, Gal P, Kroboth P, Smith H, Johnson M
Department of Medicine, Moses H. Cone Memorial Hospital, Greensboro, NC.
Int J Clin Pharmacol Ther Toxicol. 1993 Feb;31(2):100-4.
Intranasal verapamil administration may limit intrasubject variability encountered due to the metabolism differences of the d and l-isomers. We simultaneously measured verapamil/norverapamil concentrations, PR interval, heart rate (HR), and mean arterial pressure (MAP) in six healthy volunteers receiving verapamil 5 mg intranasally and intravenously on two separate occasions. Two subjects achieved measurable verapamil concentrations after intranasal administration with a mean bioavailability of 16.1%. Intranasal bioavailability was limited secondary to instillation volume. No relationship between HR, MAP and verapamil concentration was noted. A relationship between mean intravenous verapamil concentration and mean PR interval was observed; however, extensive interpatient variability existed: two subjects demonstrated enough counterclockwise hysteresis to skew mean data. Mean data may falsely represent the verapamil concentration-effect relationship. Intranasal verapamil administration is limited by instillation volume. Development of a concentrated dosage form is necessary to assess bioavailability. Concentration-effect relationships are more accurately described using individual, rather than mean data.
鼻内给予维拉帕米可能会限制因 d 型和 l 型异构体代谢差异而产生的个体内变异性。我们在六名健康志愿者身上，分两次分别经鼻内和静脉内给予 5 毫克维拉帕米，同时测量了维拉帕米/去甲维拉帕米浓度、PR 间期、心率（HR）和平均动脉压（MAP）。两名受试者在鼻内给药后达到了可测量的维拉帕米浓度，平均生物利用度为 16.1%。鼻内生物利用度受滴注量限制。未观察到 HR、MAP 与维拉帕米浓度之间的关系。观察到静脉内维拉帕米平均浓度与平均 PR 间期之间存在关系；然而，患者间存在广泛变异性：两名受试者表现出足够的逆时针滞后现象，使平均数据出现偏差。平均数据可能会错误地反映维拉帕米浓度-效应关系。鼻内给予维拉帕米受滴注量限制。开发浓缩剂型对于评估生物利用度是必要的。使用个体数据而非平均数据能更准确地描述浓度-效应关系。
