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口服泛昔洛韦或静脉输注喷昔洛韦后,喷昔洛韦在健康猫体内的药代动力学。

Pharmacokinetics of penciclovir in healthy cats following oral administration of famciclovir or intravenous infusion of penciclovir.

作者信息

Thomasy Sara M, Whittem Ted, Bales Jerry L, Ferrone Marcus, Stanley Scott D, Maggs David J

机构信息

Veterinary Medical Teaching Hospital, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616, USA.

出版信息

Am J Vet Res. 2012 Jul;73(7):1092-9. doi: 10.2460/ajvr.73.7.1092.

Abstract

OBJECTIVE

To investigate the pharmacokinetics of penciclovir in healthy cats following oral administration of famciclovir or IV infusion of penciclovir.

ANIMALS

6 cats.

PROCEDURES

Cats received famciclovir (40 [n = 3] or 90 [3] mg/kg, PO, once) in a balanced crossover-design study; the alternate dose was administered after a ≥ 2-week washout period. After another washout period (≥ 4 weeks), cats received an IV infusion of penciclovir (10 mg/kg delivered over 1 hour). Plasma penciclovir concentrations were analyzed via liquid chromatography-mass spectrometry at fixed time points after drug administration.

RESULTS

Mean ± SD maximum plasma concentration (C(max)) of penciclovir following oral administration of 40 and 90 mg of famciclovir/kg was 1.34 ± 0.33 μg/mL and 1.28 ± 0.42 μg/mL and occurred at 2.8 ± 1.8 hours and 3.0 ± 1.1 hours, respectively; penciclovir elimination half-life was 4.2 ± 0.6 hours and 4.8 ± 1.4 hours, respectively; and penciclovir bioavailability was 12.5 ± 3.0% and 7.0 ± 1.8%, respectively. Following IV infusion of penciclovir (10 mg/kg), mean ± SD penciclovir clearance, volume of distribution, and elimination half-life were 4.3 ± 0.8 mL/min/kg, 0.6 ± 0.1 L/kg, and 1.9 ± 0.4 hours, respectively.

CONCLUSIONS AND CLINICAL RELEVANCE

Penciclovir pharmacokinetics following oral administration of famciclovir were nonlinear within the dosage range studied, likely because of saturation of famciclovir metabolism. Oral administration of famciclovir at 40 or 90 mg/kg produced similar C(max) and time to C(max) values. Therefore, the lower dose may have similar antiviral efficacy to that proven for the higher dose.

摘要

目的

研究口服泛昔洛韦或静脉输注喷昔洛韦后,喷昔洛韦在健康猫体内的药代动力学。

动物

6只猫。

步骤

在一项平衡交叉设计研究中,猫接受泛昔洛韦(40 [n = 3] 或90 [3] mg/kg,口服,一次);在≥2周的洗脱期后给予另一剂量。在另一个洗脱期(≥4周)后,猫接受静脉输注喷昔洛韦(10 mg/kg,输注1小时)。给药后在固定时间点通过液相色谱 - 质谱法分析血浆喷昔洛韦浓度。

结果

口服40和90 mg泛昔洛韦/kg后,喷昔洛韦的平均±标准差最大血浆浓度(C(max))分别为1.34 ± 0.33 μg/mL和1.28 ± 0.42 μg/mL,分别在2.8 ± 1.8小时和3.0 ± 1.1小时出现;喷昔洛韦消除半衰期分别为4.2 ± 0.6小时和4.8 ± 1.4小时;喷昔洛韦生物利用度分别为12.5 ± 3.0%和7.0 ± 1.8%。静脉输注喷昔洛韦(10 mg/kg)后,喷昔洛韦的平均±标准差清除率、分布容积和消除半衰期分别为4.3 ± 0.8 mL/min/kg、0.6 ± 0.1 L/kg和1.9 ± 0.4小时。

结论及临床意义

在所研究的剂量范围内,口服泛昔洛韦后喷昔洛韦的药代动力学是非线性的,可能是由于泛昔洛韦代谢饱和所致。口服40或90 mg/kg泛昔洛韦产生相似的C(max)和达到C(max)的时间值。因此,较低剂量可能具有与较高剂量已证实的抗病毒疗效相似的效果。

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