Hammill S C, Shand D G, Harrell F E, Zimmerman J M, Reiter M J, Verghese C, Pritchett E L
Clin Pharmacol Ther. 1982 Dec;32(6):686-91. doi: 10.1038/clpt.1982.224.
The oral form of pirmenol has not been administered to man. Pirmenol was given by mouth to eight patients with chronic, stable premature ventricular beats (PVBs) to determine effective dose and kinetics. The patients were evaluated with a dose-ranging protocol following by a double-blind, crossover, placebo-controlled study of doses that were effective during dose ranging. Oral doses of 150 to 250 mg induced at least 90% suppression of PVBs 18 of the 19 times they were administered during both protocols. During the double blind experiment, a single oral dose of pirmenol suppressed 95 +/- 8% PVBs/hr (mean +/- SD) for 3 consecutive hr, while placebo suppressed 4 +/- 42% PVBs/hr (P less than 0.01). a 90% or greater reduction in PVBs persisted for a median of 6 hr (range 1 to 8 hr). The range of plasma pirmenol concentrations associated with an at last 90% reduction in PVBs was 0.7 to 2.0 micrograms/ml. Median half-life (t1/2) was 9.3 hr (range 6.0 to 12.4) with 86.6 +/- 2.4% protein binding and 82.6 +/- 23.6% bioavailability. At peak drug level there was lengthening of the QTc interval (0.036 sec, P less than 0.05), but no change in heart rate, blood pressure, PR interval or QRS duration, or symptoms. In this single-dose study, pirmenol effectively reduced PVBs, has a relatively long t1/2, and was minimally toxic.
吡美诺的口服剂型尚未用于人体。对8例慢性、稳定型室性早搏（PVBs）患者口服吡美诺，以确定有效剂量和动力学。采用剂量范围方案对患者进行评估，随后进行双盲、交叉、安慰剂对照研究，研究剂量范围期间有效的剂量。在两个方案中，口服150至250mg剂量在19次给药中有18次可使PVBs至少抑制90%。在双盲实验中，单次口服吡美诺可使PVBs每小时抑制95±8%（平均值±标准差），持续3小时，而安慰剂可使PVBs每小时抑制4±42%（P<0.01）。PVBs减少90%或更多持续的中位数为6小时（范围为1至8小时）。与PVBs至少减少90%相关的血浆吡美诺浓度范围为0.7至2.0μg/ml。中位半衰期（t1/2）为9.3小时（范围为6.0至12.4），蛋白结合率为86.6±2.4%，生物利用度为82.6±23.6%。在药物浓度峰值时，QTc间期延长（0.036秒，P<0.05），但心率、血压、PR间期或QRS时限及症状无变化。在这项单剂量研究中，吡美诺可有效减少PVBs，半衰期相对较长，毒性极小。
