PMID: 8584484Oct 1, 1995Paper

Pharmacokinetic studies of methotrexate in plasma and synovial fluid following i.v. bolus and topical routes of administration in dogs

Pharmaceutical Research
G W LuJ W McCall

Abstract

The pharmacokinetic properties of methotrexate (MTX) in the plasma and synovial fluid (SF) after bolus i.v. and topical administration were studied in dogs to assess the feasibility of topical delivery of MTX for the treatment of rheumatoid arthritis. A MTX gel in Poloxamer 407 containing an absorption enhancer was formulated and topically applied on the elbow and stifle joints of dogs. SF was collected by inserting a needle with syringe into the joint space. Drug concentrations in the plasma, SF and muscle tissues were determined using a HPLC method with fluorimetric detection. Peak MTX concentrations in SF occurred at 38 +/- 5 min following bolus i.v. dose, indicating the presence of a substantial diffusion barrier between the plasma and SF. The plasma/SF concentration ratios of 1.16 +/- 0.25 were maintained after the attainment of distribution equilibrium between the two compartments. The t1/2 values in the plasma (11.2 +/- 1.2 hr) and SF (12.7 +/- 3.7 hr) were similar during the elimination phase, while the MRT in SF (3.24 +/- 0.21 hr) was longer than that in plasma (2.56 +/- 0.20 hr), probably due to the slow distribution of MTX to SF. After topical dose, MTX concentrations in plasma reached the steady state at approximate...Continue Reading

Citations

Oct 5, 2010·Journal of Drug Targeting·Yuan GaoShen Gao
Jun 13, 2018·Journal of Veterinary Pharmacology and Therapeutics·Antoine RostangCaroline Prouillac
Jul 27, 2012·Therapeutic Delivery·Rachna Prasad, Veena Koul
Mar 26, 2010·Drug Development and Industrial Pharmacy·Yuan GaoShen Gao
Aug 14, 2012·The Journal of Gene Medicine·Ines HöfigNataša Anastasov
Nov 11, 2006·Pharmaceutical Research·Gilles DumortierJean Claude Chaumeil

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