Skip to main content
SpringerLink
Log in

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

  • Original Paper
  • Published:
European Journal of Drug Metabolism and Pharmacokinetics Aims and scope Submit manuscript

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 (T max = 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 C max cumulation observed, not different from that expected for a t 1/2 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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

LBP:

Low back pain

CNS:

Central nervous system

EPS:

Eperisone

PK:

Pharmacokinetic

GI:

Gastrointestinal

T max :

Time of maximum concentration

C max :

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

t ½ :

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

λ z :

Terminal elimination rate constant

AUC0–∞ :

Area under the plasma concentration curve extrapolated to infinity time

C last :

Last quantified concentration

ANOVA:

Analysis of variance

AUC:

Area under the plasma concentration curve

CV:

Coefficient of variation

SD:

Standard deviation

h:

Hour

References

  • Beltrame A, Grangiè S, Guerra L (2008) Clinical experience with eperisone in the treatment of acute low back pain. Minerva Med 99:347–352

    PubMed  CAS  Google Scholar 

  • Bresolin N, Zucca C, Pecori A (2009a) Efficacy and tolerability of eperisone in patients with spastic palsy: a cross-over, placebo-controlled, dose-ranging trial. Eur Rev Med Pharmacol Sci 13:365–370

    PubMed  CAS  Google Scholar 

  • Bresolin N, Zucca C, Pecori A (2009b) Efficacy and tolerability of eperisone and baclofen in spastic palsy: a double-blind randomized trial. Adv Ther 26:1–6

    Article  Google Scholar 

  • Cabitza P, Randelli P (2008) Efficacy and safety of eperisone in patients with low back pain: a double blind randomized study. Eur Rev Med Pharmacol Sci 12:229–235

    PubMed  CAS  Google Scholar 

  • Di Iorio D, Henley E, Doughty A (2000) A survey of primary care physician practice patterns and adherence to acute low back problem guidelines. Arch Fam Med 9(10):1015–1021

    Article  PubMed  CAS  Google Scholar 

  • Elder NC (1991) Abuse of skeletal muscle relaxants. Am Fam Physician 44:1223–1226

    PubMed  CAS  Google Scholar 

  • Fujioka M, Kuriyama H (1985) Eperisone, an antispastic agent, possesses vasodilating actions on the guinea-pig basilar artery. J Pharmacol Exp Ther 235:757–763

    PubMed  CAS  Google Scholar 

  • Ito T, Hori M, Furukaa K, Karasawa T, Kadokawa T (1985) Pharmacological studies of 1-(2, 3-dimethyl-4-mthoxyphenyl)-2-methyl-3-(1-pyrrolidinyl)-1-propanone hydrochloride (AD-2239), a centrally acting muscle relaxant. Arch Int Pharmacodyn 275:105–122

    PubMed  CAS  Google Scholar 

  • Iwase S, Mano T, Saito M, Ishida G (1992) Effect of a centrally-acting muscle relaxant, eperisone hydrochloride, on muscle sympathetic nerve activity in humans. Funct Neurol 7:459–470

    PubMed  CAS  Google Scholar 

  • Kocsis P, Farkas S, Fodor L, Bielik N, Than M, Kolok S, Gere A, Csejtei M, Tarnawaet I (2005) Tolperisone-type drugs inhibit spinal reflexes via blockade of voltage-gated sodium and calcium channels. J Pharmacol Exp Ther 315:1237–1246

    Article  PubMed  CAS  Google Scholar 

  • Li D, Xin W, Shengqiang Z, Jianpin S, Yindi Z (2004) Rapid and sensitive liquid chromatography–electrospray ionization-mass spectrometry method for the determination of eperisone in human plasma: method and clinical applications. J Chromatogr Sci 42:254–258

    Google Scholar 

  • Marchettini P, Pecori A (2009) Eperisone cloridrato versus baclofene nel trattamento a lungo termine della paralisi spastica: uno studio randomizzato in doppio cieco. Therapeutic Evidence Based Giugno 2(3). http://www.wkhealth.it/teb/default.asp. Accessed 6 July

  • Min Kyo J, Eun Sook J, Nam Hee K, Chang-Soo K, Youn-Bok C, Yong-Moon L, Su-Youn A, Hwang-Eui C, Yong Hwa L, Jin Tat H, Gong-Cheul M (2007) Determination of eperisone in human plasma by liquid chromatography–ESI-tandem mass spectrometry. Arch Pharm Res 30:1174–1178

    Article  Google Scholar 

  • Morikawa K, Oshita M, Yamazaki M, Ohara N, Kato H, Ito Y, Kontani H, Koshiura R (1987) Pharmacological studies of the new centrally acting muscle relaxant 4’-ethyl-2-methyl-3-pyrrolidinopropiophenone hydrochloride. Arzneim Forsch Drug Res 37:331–336

    CAS  Google Scholar 

  • RxList, the Internet Drug Index (2010). Web address: http://www.rxlist.com/script/main/hp.asp. Accessed on January 8

  • Sakai Y, Matsuyama Y, Nakamura H et al (2008) The effect of muscle relaxant on the paraspinal muscle blood flow: a randomized controlled trial in patients with chronic low back pain. Spine 33:581–587

    Article  PubMed  Google Scholar 

  • Sartini S (2008) Open experience with a new myorelaxant agent for low back pain. Adv Ther 25:1–9

    Article  Google Scholar 

  • Takamatsu T, Yamazaki K, Kayano M, Takenaka F, Hasui M, Okhawa T (1992) Determination of eperisone in human plasma by gas chromatography-mass spectrometry. J Chromatogr 584:261–266

    Article  PubMed  CAS  Google Scholar 

  • Tariq M, Akhtar N, Alì M, Rao S, Badshah M, Irshad M (2005) Eperisone compared to physiotherapy on muscular tone of stroke patients: a prospective randomized open study. J Pak Med Assoc 55:202–204

    PubMed  Google Scholar 

  • Trellu M, Filali-Ansary A, Françon D, Adam R, Lluel P, Dubruc C, Thénot JP (2004) New metabolic and pharmacokinetic characteristics of thiocolchicoside and its active metabolite in healthy humans. Fundam Clin Pharmacol 18:493–501

    Article  PubMed  CAS  Google Scholar 

  • Viladot Pericé R, Rodriguez Boronat E, Ferrer Bosch F, Rusinyol FC (2008) Myorelaxant effects of eperisone and diazepam in the treatment of acute spinal muscle contracture: a comparative study. J Anaesth Clin Pharmacol 24:285–290

    Google Scholar 

  • Wuis EW, Dirks MJM, Vree TB, Van der Kleijn E (1990) Pharmacokinetics of baclofen in spastic patients receiving multiple oral doses. Pharm Weekbl (sci) 12:71–74

    CAS  Google Scholar 

Download references

Acknowledgments

We thank Dr. Giacomo Spignoli for his kind help.

Author information

Authors and Affiliations

  1. Pharmacokinetic Unit, Unifarm Research Center, University of Catania, Viale A. Doria 21, 95125, Catania, Italy

    Barbara Melilli, Cateno Piazza, Daniela Cristina Vitale & Maria Rosa Marano

  2. Eisai, Via dell’Unione Europea 6b, 20097, San Donato Milanese Milano, Italy

    Andrea Pecori

  3. Alfa Wassermann, Via Ragazzi del ‘99 n 5, 65020, Bologna, Italy

    Paolo Mattana

  4. PhD School of Neuropharmacology, University of Catania, Viale A. Doria 6, 95125, Catania, Italy

    Valentina Li Volsi & Carmelo Iuculano

  5. Polyclinic Vittorio Emanuele University of Catania, Viale S. Sofia 78, 95123, Catania, Italy

    Francesco Cardì

  6. Department of Experimental and Clinical Pharmacology, University of Catania, Viale A. Doria 6, 95125, Catania, Italy

    Filippo Drago

Authors
  1. Barbara Melilli
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Cateno Piazza
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Daniela Cristina Vitale
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Maria Rosa Marano
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Andrea Pecori
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Paolo Mattana
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Valentina Li Volsi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Carmelo Iuculano
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Francesco Cardì
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Filippo Drago
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Filippo Drago.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Melilli, B., Piazza, C., Vitale, D.C. et al. Human pharmacokinetics of the muscle relaxant, eperisone hydrochloride by liquid chromatography–electrospray tandem mass spectrometry. Eur J Drug Metab Pharmacokinet 36, 71–78 (2011). https://doi.org/10.1007/s13318-011-0034-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13318-011-0034-0

Keywords

Search

Navigation