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Pharmacokinetic and biodistribution study of eserine and pralidoxime chloride in rabbits following a single application of a transdermal patch

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Abstract

In the present study, a simple reverse-phase high-performance liquid chromatography method with diode array detection has been developed and validated for the simultaneous determination and quantification of eserine and pralidoxime chloride in rabbit plasma and its application to pharmacokinetic study. The pharmacokinetic study was performed after transdermal application of single patch in rabbits. The plasma levels of both drugs following transdermal application of single patch were maintained for 72 h after removal of the patch. The maximal concentrations (C max) of both drugs were significantly reduced while the mean areas under the plasma concentration vs. time moment curve and mean residence times were evidently increased and extended, respectively. A sustained activity was observed over a period of 3 days. This sustained activity was due to the controlled release of drug into the systemic circulation following transdermal application. Linear correlation was also observed when fraction of drug permeated was correlated with the fraction of drug absorbed at the same time point. Gamma scintigraphy imaging on rabbit following transdermal patch application was performed to ascertain the localization of drugs in rabbit brain.

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Abbreviations

% v/v:

Percentage of volume by volume

°C:

Degree Celsius

µg/mL:

Microgram per milliliter

µL:

Microliter

µm:

Micrometer

2-PAM:

Pralidoxime chloride

AUC:

Area under curve

AUMC:

Area under moment curve

BBB:

Blood–brain barrier

C max :

Peak plasma concentration

C t :

Concentration of drug in time t

DIA:

Drug-in-adhesive

DAD:

Diode array detector

EDTA:

Ethylene diamine tetra acetic acid

FDA:

Food and drug administration

F t :

Fraction of drug permeated in time t

Gm:

Gram

h:

Hour

IS:

Internal standard

ITLC:

Instant thin-layer chromatography

i.d:

Internal diameter

K el :

Elimination rate constant

LOD:

Limit of detection

LLOQ:

Lower limit of quantification

LOQ:

Limit of quantification

LQC:

Lower quality control

MQC:

Middle quality control

HQC:

Higher quality control

mg:

Milligram

Min:

Minute

mm:

Millimolar

MRT:

Mean residential time

mL:

Milliliter

ng/mL:

Nanogram per milliliter

nm:

Nanometer

p H :

Negative logarithm of hydrogen ion concentration

PSAs:

Pressure-sensitive adhesives

PK:

Pharmacokinetic

QC:

Quality control

RPM:

Revolution per minute

R.S.D:

Relative standard deviation

R 2 :

Correlation coefficient

RP-HPLC:

Reverse-phase high-performance liquid chromatography

SD:

Standard deviation

t 1/2 :

Elimination half-life

TDDS:

Transdermal drug delivery system

T max :

Time taken to reach peak plasma concentration

TC:

Technetium

UV:

Ultra-violet

Ver:

Version

vs.:

Versus

λ max :

Maximum wavelength

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Acknowledgments

One of the authors Subham Banerjee is grateful to Defence Research and Development Organisation, Ministry of Defence, Govt. of India for providing the research fellowship for this work. Subham Banerjee is also thankful to Defence Research Laboratory, Tezpur, Assam, India for providing necessary instrumental facilities for this research work and the administration of the Birla Institute of Technology, Mesra, Ranchi, India for providing necessary administrative support for carrying out his Ph.D work. The authors declare that they have no conflicts of interest to declare in connection with the contents of this manuscript.

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Authors and Affiliations

  1. Division of Pharmaceutical Technology, Defence Research Laboratory, Post Bag No: 2, Tezpur, 784 001, Assam, India

    Subham Banerjee, Pronobesh Chattopadhyay & Vijay Veer

  2. Department of Pharmaceutical Sciences, Birla Institute of Technology, Mesra, Ranchi, 835 215, Jharkhand, India

    Subham Banerjee & Animesh Ghosh

  3. Department of Nuclear Medicine, Institute of Nuclear Medicine and Allied Sciences, Brig. SK Mazumdar Road, Delhi, 110054, India

    Aseem Bhatnagar

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  1. Subham Banerjee
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  2. Pronobesh Chattopadhyay
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  5. Vijay Veer
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Correspondence to Subham Banerjee.

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Banerjee, S., Chattopadhyay, P., Ghosh, A. et al. Pharmacokinetic and biodistribution study of eserine and pralidoxime chloride in rabbits following a single application of a transdermal patch. Eur J Drug Metab Pharmacokinet 41, 219–230 (2016). https://doi.org/10.1007/s13318-014-0250-5

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