Mason W D, Lanman R C, Kirsten E B
J Pharm Sci. 1987 Jun;76(6):437-40. doi: 10.1002/jps.2600760605.
Twenty-four healthy male subjects were administered 300 mg of propafenone every 8 h for 6 d in each of two phases that were separated by 2 d. Plasma samples were collected during the approach to steady state for each phase, and plasma and saliva samples were collected frequently at steady state. Both plasma and saliva propafenone were assayed by a specific HPLC method. Two estimates of elimination half-life (t1/2), mean steady-state concentration (CPss), time to maximal concentration (tmax), and maximal concentration (CPmax) were estimated for each subject. Also mean steady-state saliva concentrations (CSss), time to maximal saliva concentration (tSmax), and maximal saliva concentrations (CSmax) were estimated. A large intersubject variance in both t1/2 and CPss were observed in the 24 subjects, with the t1/2 values ranging from 2.1 to 27.2 h and the CPss values from 0.3 to 3.03 microgram/mL. Each subject was quite consistent for the two phases, suggesting a relatively low intrasubject variance for propafenone kinetics. A histogram shows most subjects to have t1/2 values between 2 and 10 h, with diminishing numbers of subjects at greater t1/2 values rather than a bimodal distribution. Saliva concentrations ranged from 12 to 72% of the corresponding plasma concentrations, being 24.7 +/- 11.1% of the simultaneously collected plasma sample overall (mean +/- SD). a significant (p less than 0.001) positive correlation exists between CPss and CSss.
24名健康男性受试者在两个阶段中，每个阶段每隔8小时服用300毫克普罗帕酮，持续6天，两个阶段间隔2天。在每个阶段接近稳态时采集血浆样本，并在稳态时频繁采集血浆和唾液样本。血浆和唾液中的普罗帕酮均采用特定的高效液相色谱法进行测定。对每个受试者估计了消除半衰期（t1/2）、平均稳态浓度（CPss）、达峰时间（tmax）和最大浓度（CPmax）的两个值。还估计了平均稳态唾液浓度（CSss）、达最大唾液浓度时间（tSmax）和最大唾液浓度（CSmax）。在24名受试者中观察到t1/2和CPss的受试者间差异很大，t1/2值范围为2.1至27.2小时，CPss值范围为0.3至3.03微克/毫升。每个受试者在两个阶段相当一致，表明普罗帕酮动力学的受试者内差异相对较低。直方图显示，大多数受试者的t1/2值在2至10小时之间，t1/2值越大受试者数量越少，而非双峰分布。唾液浓度为相应血浆浓度的12%至72%，总体上是同时采集的血浆样本的24.7±11.1%（平均值±标准差）。CPss与CSss之间存在显著（p<0.001）正相关。
