Pharmacokinetic Study of Ketoprofen Isopropyl Ester-Loaded Lipid Microspheres in Rat Blood Using Microdialysis

Abstract

A blood microdialysis technique coupled with high-performance liquid chromatography was used to investigate the pharmacokinetics of unbound ketoprofen in rats after intravenous administration of a lipid-soluble ketoprofen derivate, ketoprofen isopropyl ester (KPI), loaded into lipid microspheres (LM) and ketoprofen solution. A microdialysis probe was inserted into the jugular vein of male Wistar rats. KPI-loaded LM or ketoprofen solution (24 mg/kg, i.v.) was then administrated via a femoral vein. Dialysate samples were analyzed using HPLC. The in vitro and in vivo recovery rate of the microdialysis probe was 30.42؎0.74% (n‫)3؍‬ and 40.27؎2.74% (n‫,)3؍‬ respectively. The pharmacokinetic parameters for ketoprofen after intravenous administration of KPIloaded LM and ketoprofen solution exhibited no statistically significant differences. The results of this pharmacokinetic study indicate that the microdialysis technique can be widely applicable to investigations of in vivo freedrug of microcarrier systems.

Nano‐LC‐MS/MS for the monitoring of angiotensin IV in rat brain microdialysates: Limitations and possibilities

“…It is, indeed, generally known that in vitro calibration often does not correlate well to in vivo calibration because of differences between the external media resistance of tissue and aqueous solutions [23]. A higher in vivo recovery was already described in previous papers [18,21,24,25]. This feature cannot be explained by a passive diffusion model but is accounted for in a model that incorporates active processes, microvasculature transport, metabolism, release, and uptake [18].…”

Pulmonary Selectivity and Local Pharmacokinetics of Ambroxol Hydrochloride Dry Powder Inhalation in Rat

“…Then the probes were perfused with Ringer's solution containing AH (1, 5 or 10 µg/mL) at a flow rate of 4 µL/min. The in vivo recovery rate of AH was calculated from the following equation: R dial = 1 − C dial / C perf ,21 where R dial is the AH in vivo recovery rate, C perf is the concentration of AH in the perfusate, and C dial is the concentration of AH in the dialysate.…”

Rapid online-SPE-MS/MS method for ketoprofen determination in dermal interstitial fluid samples from rats obtained by microdialysis or open-flow microperfusion

“…Analysis of MD samples is often performed without any sample processing [15,16,19] because MD samples generally have a very low protein content due to the passage of the sample through a membrane. However, for open-flow microperfusion sampling is performed through macroscopic holes, resulting in the presence of considerable amounts of proteins.…”

“…However, even sample volumes of 20 l can be difficult to obtain for analysis as mentioned above. Moreover, microdialysis provides relatively clean and almost protein-free samples which are commonly analyzed without further clean-up procedures [15,16]. In contrast, samples acquired by open-flow microperfusion are expected to contain a higher amount of proteins owing to stable sampling of large molecules such as albumin, as has been reported in the literature [7].…”

“…However, two papers on microdialysis studies of ketoprofen do include limited information on the method of analysis used. He et al [15] used an isocratic HPLC-UV method for ketoprofen analysis in blood microdialysis and plasma samples with run times of 8 min. Twenty microliters extract from 200 l plasma is injected, however the authors did not state how much microdialysis sample is needed for direct injection into the HPLC-UV system.…”