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局部、口服和静脉给药后马体内二甲基亚砜(DMSO)的药代动力学、分布及血浆浓度。

Pharmacokinetics, disposition, and plasma concentrations of dimethyl sulfoxide (DMSO) in the horse following topical, oral, and intravenous administration.

作者信息

Soma L R, Robinson M A, You Y, Boston R C, Rudy J

机构信息

School of Veterinary Medicine, New Bolton Center Campus, University of Pennsylvania, Kennett Square, PA, USA.

Pennsylvania Equine Toxicology & Research Center, West Chester University, West Chester, PA, USA.

出版信息

J Vet Pharmacol Ther. 2018 Jun;41(3):384-392. doi: 10.1111/jvp.12476. Epub 2018 Jan 14.

Abstract

Compartmental models were used to investigate the pharmacokinetics of intravenous (i.v.), oral (p.o.), and topical (TOP) administration of dimethyl sulfoxide (DMSO). The plasma concentration-time curve following a 15-min i.v. infusion of DMSO was described by a two-compartment model. Median and range of alpha (t ) and beta (t ) half-lives were 0.029 (0.026-0.093) and 14.1 (6.6-16.4) hr, respectively. Plasma concentration-time curves of DMSO following p.o. and TOP administration were best described by one-compartment absorption and elimination models. Following the p.o. administration, median absorption (t ) and elimination (t ) half-lives were 0.15 (0.01-0.77) and 15.5 (8.5-25.2) hr, respectively. The plasma concentrations of DMSO were 47.4-129.9 μg/ml, occurring between 15 min and 4 hr. The fractional absorption (F) during a 24-hr period was 47.4 (22.7-98.1)%. Following TOP administrations, the median t and t were 1.2 (0.49-2.3) and 4.5 (2.1-11.0) hr, respectively. Plasma concentrations were 1.2-8.2 μg/ml occurring at 2-4 hr. Fractional absorption following TOP administration was 0.48 (0.315-4.4)% of the dose administered. Clearance (Cl) of DMSO following the i.v. administration was 3.2 (2.2-6.7) ml hr  kg . The corrected clearances (Cl ) for p.o. and TOP administrations were 2.9 (1.1-5.5) and 4.5 (0.52-18.2) ml hr  kg .

摘要

采用房室模型研究了二甲基亚砜(DMSO)静脉注射(i.v.)、口服(p.o.)和局部给药(TOP)后的药代动力学。静脉输注DMSO 15分钟后的血浆浓度-时间曲线用二室模型描述。α(t)和β(t)半衰期的中位数及范围分别为0.029(0.026 - 0.093)小时和14.1(6.6 - 16.4)小时。口服和局部给药后DMSO的血浆浓度-时间曲线用一室吸收和消除模型描述最佳。口服给药后,吸收(t)和消除(t)半衰期的中位数分别为0.15(0.01 - 0.77)小时和15.5(8.5 - 25.2)小时。DMSO的血浆浓度在15分钟至4小时之间为47.4 - 129.9μg/ml。24小时内的吸收分数(F)为47.4(22.7 - 98.1)%。局部给药后,t和t的中位数分别为1.2(0.49 - 2.3)小时和4.5(2.1 - 11.0)小时。血浆浓度在2 - 4小时为1.2 - 8.2μg/ml。局部给药后的吸收分数为给药剂量的0.48(0.315 - 4.4)%。静脉给药后DMSO的清除率(Cl)为3.2(2.2 - 6.7)ml·hr⁻¹·kg⁻¹。口服和局部给药的校正清除率(Cl)分别为2.9(1.1 - 5.5)和4.5(0.52 - 18.2)ml·hr⁻¹·kg⁻¹。

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