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目的研究性腺机能低下患者单次和多次外用睾酮贴剂的药代动力学和药效学。方法用多剂量、三周期、剂量递增、连续给药设计方案,12名原发性或继发性性腺机能低下的中国男性受试者外用2,4,6贴睾酮贴剂,用化学发光免疫试剂盒方法测定血清总睾酮浓度,计算其主要药代动力学参数。结果 7名受试者完成全部试验,单次外用2,4,6贴睾酮贴剂的主要药代动力学参数分别如下:Cmax为(5.65±3.47),(30.13±47.59),(37.64±41.55)nmoL.L-1;Tmax为(10.86±2.54),(8.00±1.63),(10.86±5.98)h;AUC0-t为(91.96±62.49),(197.01±144.75),(321.49±172.82)nmoL.h.L-1。多次外用睾酮贴剂后,血清总睾酮的主要药代动力学参数分别如下:Csmsax为(6.74±5.12),(16.89±11.15),(36.13±44.32)nmoL.L-1;Tmax为(8.86±3.44),(5.71±2.93),(7.71±2.43)h;AUC0ss-t为(110.92±60.49),(238.72±104.26),(416.62±278.66)nmoL.h.L-1。结论总睾酮的Cmax和AUC0-t随给药剂量的增加而增大。多次外用睾酮6贴后0～24 h血清总睾酮浓度均达到正常值范围。
Objective To study the pharmacokinetics and pharmacodynamics of single and multiple topical testosterone patches in patients with hypogonadism. Methods A total of 12 Chinese male subjects with primary or secondary hypogonadism were treated with topical 2,4,6-labeled testosterone patch by multi-dose, three-cycle, dose-escalation and continuous dose design. Chemiluminescent immunoassay Kit method for the determination of total serum testosterone concentration, calculate the main pharmacokinetic parameters. Results Seven of the subjects completed all the trials. The main pharmacokinetic parameters of single external topical 2,4,6-labeled testosterone patch were as follows: Cmax was (5.65 ± 3.47), (30.13 ± 47.59), (37.64 ± 41.55 ) (n = 100), nmax (n = 10), n = 10 and n = .hL-1. The main pharmacokinetic parameters of total testosterone in serum after repeated topical testosterone patches were as follows: Csmsax was (6.74 ± 5.12), (16.89 ± 11.15), (36.13 ± 44.32) nmoL.L-1; Tmax was (8.86 ± 3.44, 5.71 ± 2.93 and 7.71 ± 2.43 h respectively; AUC0ss-t was (110.92 ± 60.49), (238.72 ± 104.26) and (416.62 ± 278.66) nmoL.hL-1, respectively. Conclusion The Cmax and AUC0-t of total testosterone increase with the increase of dose. Repeated topical testosterone 6 posted 0 ~ 24 h serum total testosterone concentrations reached the normal range.