Jones Terry M, Ellman Herman, deVries Tina
J Drugs Dermatol. 2017 Oct 1;16(10):1022-1028.
To characterize minocycline pharmacokinetics and relative bioavailability following multiple-dose topical administration of minocycline hydrochloride (HCl) foam 4% (FMX101 4%) as compared with single-dose oral administration of minocycline HCl extended-release tablets (Solodyn®) in subjects with moderate-to-severe acne.
A Phase 1, single-center, nonrandomized, open-label, active-controlled, 2-period, 2-treatment crossover clinical study. The study included 30 healthy adults (mean age, 22.6 years; 90% white, and 60% females) who had moderate-to-severe acne. Subjects were assigned to first receive a single oral dose of a minocycline HCl extended-release tablet (approximately 1 mg/kg). At 10 days after the oral minocycline dose, topical minocycline foam 4% was applied, once daily for 21 days. Serial blood samples were obtained before and after administration of oral minocycline and each topical application of minocycline foam 4% on days 1, 12, and 21.
Following oral administration of minocycline (approximately 1 mg/kg), plasma minocycline concentration increased until 3 hours, followed by a log-linear decrease over the remainder of the 96-hour sampling period. Following topical application of a 4-g maximal-use dose of minocycline foam 4% for 21 days, plasma minocycline concentration was very low, with geometric mean Cmax values ranging from 1.1 ng/mL to 1.5 ng/mL. Steady state was achieved by day 6. Overall, minocycline exposure with topical minocycline foam 4% was 730 to 765 times lower than that with oral minocycline. There was no evidence of minocycline accumulation over the 21 days of topical application of minocycline foam 4%. Topical minocycline foam 4% appeared to be safe and well tolerated, with no serious treatment-emergent adverse events (TEAEs), treatment-related TEAEs, or TEAEs that led to treatment discontinuation.
Once-daily topical application of minocycline foam 4% did not lead to significant systemic exposure to minocycline. It appears to be a well-tolerated treatment option for individuals with moderate-to-severe acne.
J Drugs Dermatol. 2017;16(10):1022-1028.
.对比4%盐酸米诺环素泡沫剂（FMX101 4%）多剂量局部给药与盐酸米诺环素缓释片（Solodyn®）单剂量口服给药后，中度至重度痤疮患者的米诺环素药代动力学及相对生物利用度。
一项1期、单中心、非随机、开放标签、活性对照、2期、2治疗交叉临床研究。该研究纳入了30名患有中度至重度痤疮的健康成年人（平均年龄22.6岁；90%为白人，60%为女性）。受试者首先接受单剂量口服盐酸米诺环素缓释片（约1 mg/kg）。在口服米诺环素剂量10天后，应用4%米诺环素泡沫剂，每日1次，共21天。在口服米诺环素给药前后以及在第1、12和21天每次局部应用4%米诺环素泡沫剂后采集系列血样。
口服米诺环素（约1 mg/kg）后，血浆米诺环素浓度在3小时内升高，随后在96小时采样期的剩余时间呈对数线性下降。局部应用4%米诺环素泡沫剂最大使用剂量4 g，持续21天，血浆米诺环素浓度非常低，几何平均Cmax值在1.1 ng/mL至1.5 ng/mL范围内。在第6天达到稳态。总体而言，4%米诺环素泡沫剂局部给药的米诺环素暴露量比口服米诺环素低730至765倍。在4%米诺环素泡沫剂局部应用的21天内，没有米诺环素蓄积的证据。4%米诺环素泡沫剂似乎安全且耐受性良好，没有严重的治疗中出现的不良事件（TEAE）、与治疗相关的TEAE或导致治疗中断的TEAE。
每日1次局部应用4%米诺环素泡沫剂不会导致米诺环素显著的全身暴露。对于中度至重度痤疮患者，它似乎是一种耐受性良好的治疗选择。
《药物皮肤病学杂志》。2017年；16(10):1022 - 1028。
