Human pharmacokinetics of the muscle relaxant, eperisone hydrochloride by liquid chromatography–electrospray tandem mass spectrometry

  • Barbara Melilli
  • Cateno Piazza
  • Daniela Cristina Vitale
  • Maria Rosa Marano
  • Andrea Pecori
  • Paolo Mattana
  • Valentina Li Volsi
  • Carmelo Iuculano
  • Francesco Cardì
  • Filippo Drago
Original Paper

Abstract

Eperisone hydrochloride (4′-ethyl-2-methyl-3-piperidinopropiophenone hydrochloride) is a muscle relaxant agent, widely used in the treatment of patients with muscular contractures, low back pain or spasticity. Because of its mechanism of action (inhibition of gamma-efferent firing and local vasodilatation activity), side effects on central nervous system are rarely observed. A sensitive liquid chromatography–electrospray ionization-mass spectrometry method for determination of eperisone in human plasma has been developed, with a lower limit of quantification of 0.01 ng/mL. The method was applied to a pharmacokinetic study in 12 healthy volunteers given eperisone 100 mg as single dose on day 1 and three times daily on days 2 to 4. Eperisone was rapidly absorbed after oral administration (Tmax = 1.6 h) as it was expected by its fast-onset relaxant activity. Moreover, eperisone underwent a rapid elimination from the body (biological half-life 1.87 h), which was not modified during the repeated dosing as suggested by the Cmax cumulation observed, not different from that expected for a t1/2 of 1.87 h as suggested by the similar and negligible plasma concentration values (0.063 and 0.067 ng/mL) measured on day 4 before the morning dose and 12 h after evening dose, thus ruling out any potential risk for drug accumulation. Thus, the pharmacokinetic characteristics of eperisone provide further justification for its tolerability in patients with low back pain or spastic palsy, in which the drug is given for periods ranging from few days to several months, respectively.

Keywords

Eperisone Pharmacokinetics Tandem mass spectrometry Human plasma 

Abbreviations

LBP

Low back pain

CNS

Central nervous system

EPS

Eperisone

PK

Pharmacokinetic

GI

Gastrointestinal

Tmax

Time of maximum concentration

Cmax

Maximum plasma concentration

ng

Nanogram

mL

Millilitre

mg

Milligram

LLOQ

Lower limits of quantification

LC–MS/MS

Liquid chromatography–mass spectrometry triple quadrupole mass spectrometry

UCMC

University of Catania Medical Center

GCP

Good clinical practice

ECG

Electrocardiogram

HBV

Hepatitis B virus

HCV

Hepatitis C virus

HIV

Human immunodeficiency virus

t½

Plasma concentration half-life

SPC

Summary of product characteristics

rpm

Revolutions per minute

min

minute

HPLC

High performance liquid chromatography

ESI

Electrospray ionization

TOL

Tolperisone

µl

Microliter

mM

Millimole

v/v

Volume to volume

m/z

Mass to charge

AUC0–t

Area under the plasma concentration curve administration to last observed concentration at time t

λz

Terminal elimination rate constant

AUC0–∞

Area under the plasma concentration curve extrapolated to infinity time

Clast

Last quantified concentration

ANOVA

Analysis of variance

AUC

Area under the plasma concentration curve

CV

Coefficient of variation

SD

Standard deviation

h

Hour

Notes

Acknowledgments

We thank Dr. Giacomo Spignoli for his kind help.

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Copyright information

© Springer-Verlag France 2011

Authors and Affiliations

  • Barbara Melilli
    • 1
  • Cateno Piazza
    • 1
  • Daniela Cristina Vitale
    • 1
  • Maria Rosa Marano
    • 1
  • Andrea Pecori
    • 2
  • Paolo Mattana
    • 3
  • Valentina Li Volsi
    • 4
  • Carmelo Iuculano
    • 4
  • Francesco Cardì
    • 5
  • Filippo Drago
    • 6
  1. 1.Pharmacokinetic Unit, Unifarm Research CenterUniversity of CataniaCataniaItaly
  2. 2.EisaiSan Donato Milanese MilanoItaly
  3. 3.Alfa WassermannBolognaItaly
  4. 4.PhD School of NeuropharmacologyUniversity of CataniaCataniaItaly
  5. 5.Polyclinic Vittorio Emanuele University of CataniaCataniaItaly
  6. 6.Department of Experimental and Clinical PharmacologyUniversity of CataniaCataniaItaly

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