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Pharmacokinetics and bioavailability of tolfenamic acid in sheep
Author(s) -
Corum Orhan,
Corum Duygu Durna,
Er Ayse,
Yildiz Ramazan,
Uney Kamil
Publication year - 2018
Publication title -
journal of veterinary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.527
H-Index - 60
eISSN - 1365-2885
pISSN - 0140-7783
DOI - 10.1111/jvp.12702
Subject(s) - bioavailability , pharmacokinetics , chemistry , crossover study , tolerability , volume of distribution , pharmacology , half life , high performance liquid chromatography , chromatography , medicine , adverse effect , alternative medicine , pathology , placebo
The pharmacokinetics, bioavailability, and tolerability of tolfenamic acid ( TA ) were determined after treating sheep with TA via different routes and doses. This crossover study was carried out with a washout period of 15 days. In the study, 16 clinically healthy sheep were randomly assigned to two equal groups. In the first group ( n = 8), animals received TA by intravenous ( IV ), intramuscular ( IM ), subcutaneous ( SC ), or oral ( OR ) routes at 2 mg/kg. In the second group ( n = 8), TA was administered intravenously to each sheep at 2, 4, 8, and 16 mg/kg. Plasma samples were analyzed with a high‐performance liquid chromatography assay. Noncompartmental pharmacokinetic analyses were used to evaluate the data. The area under the concentration–time curves ( AUC 0−∞ ), elimination half‐life ( t 1/2ʎz ), and the mean residence time ( MRT ) significantly differed among the administration routes at 2 mg/kg of TA . Following IM , SC , and OR administrations, TA demonstrated different peak concentrations ( C max ) and time to reach C max ( T max ), with a bioavailability of 163%, 127%, and 107%, respectively. The dose‐normalized AUC 0−∞ revealed a significant difference among the dose groups; however, the relationship between dose and AUC 0−∞ was linear. Both t 1/2ʎz and MRT increased depending on the dose. Although the total clearance (Cl T ) decreased depending on dose, the volume of distribution at steady‐state ( V ss ) increased. Tolfenamic acid indicated a long half‐life and high bioavailability following IM , SC , and OR administrations at 2 mg/kg. TA exhibited linear kinetics and was well tolerated by the animals, except at 16 mg/kg. Thus, TA may be used in different routes and doses (≤8 mg/kg) in sheep; however, further studies are needed to determine the clinical efficacy of TA during the inflammatory and painful conditions and the pharmacokinetics and safety of repeated administration in sheep.