Thomasy Sara M, Covert Jill C, Stanley Scott D, Maggs David J
Veterinary Medical Teaching Hospital, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616, USA.
Vet Ophthalmol. 2012 Sep;15(5):299-306. doi: 10.1111/j.1463-5224.2011.00984.x. Epub 2012 Feb 16.
To validate a means of collecting tears from cats, develop an assay for quantifying famciclovir and penciclovir in tears, and to assess famciclovir and penciclovir concentrations and pharmacokinetics in the tears of cats being treated orally with famciclovir for suspected herpetic disease.
Seven client-owned cats.
Cats were treated orally with a median (range) dose of 40 (39-72) mg of famciclovir/kg three times daily for at least 24 h. At various time points following famciclovir administration, tear samples were collected using Schirmer tear test strips. Tear famciclovir and penciclovir concentrations were measured using liquid chromatography-mass spectrometry, and concentration-time profiles were analyzed noncompartmentally. The relationship between famciclovir dose and tear penciclovir concentration near its maximum was evaluated using least squares linear regression.
Maximum tear famciclovir concentration of 0.305 μg/mL occurred at 2.64 h; elimination half-life was 2.28 h. Maximum tear penciclovir concentration (0.981 μg/mL) occurred 2.25 h following oral administration of famciclovir; elimination half-life was 2.77 h. A significant positive correlation was noted between famciclovir dose and tear penciclovir concentration at various time points between 0.5 and 3.75 h following drug administration (P = 0.025). Tear penciclovir concentration exceeded the concentration shown to have in vitro efficacy against feline herpesvirus (FHV-1) (0.304 μg/mL) in about half of samples collected.
Oral administration of 40 mg of famciclovir/kg to cats resulted in a tear penciclovir concentration-time profile that approximated the plasma penciclovir concentration-time profile and frequently achieved a penciclovir concentration at the ocular surface likely to be effective against FHV-1.
验证一种从猫收集眼泪的方法,开发一种测定眼泪中泛昔洛韦和喷昔洛韦含量的分析方法,并评估口服泛昔洛韦治疗疑似疱疹性疾病的猫眼泪中泛昔洛韦和喷昔洛韦的浓度及药代动力学。
7只客户拥有的猫。
猫口服泛昔洛韦,中位(范围)剂量为40(39 - 72)mg/kg,每日3次,至少持续24小时。在给予泛昔洛韦后的不同时间点,使用泪液分泌试验试纸条收集泪液样本。采用液相色谱 - 质谱法测定泪液中泛昔洛韦和喷昔洛韦的浓度,并对浓度 - 时间曲线进行非房室分析。使用最小二乘线性回归评估泛昔洛韦剂量与接近其最大值时泪液中喷昔洛韦浓度之间的关系。
泪液中泛昔洛韦的最大浓度为0.305μg/mL,出现在2.64小时;消除半衰期为2.28小时。口服泛昔洛韦后2.25小时出现泪液中喷昔洛韦的最大浓度(0.981μg/mL);消除半衰期为2.77小时。给药后0.5至3.75小时的不同时间点,泛昔洛韦剂量与泪液中喷昔洛韦浓度之间存在显著正相关(P = 0.025)。在收集的约一半样本中,泪液中喷昔洛韦的浓度超过了显示对猫疱疹病毒(FHV - 1)具有体外疗效的浓度(0.304μg/mL)。
给猫口服40mg/kg泛昔洛韦后,泪液中喷昔洛韦的浓度 - 时间曲线与血浆中喷昔洛韦的浓度 - 时间曲线相近,且眼表喷昔洛韦浓度常达到可能对FHV - 1有效的水平。