Comparison of intrathecal concentrations of acyclovir following epidural and intravenous administration in rats

Jae Hun Kim, Mi Kyoung Lee, Jung Eun Kim, Se Hee Kim, Sang Sik Choi

Research output: Contribution to journalArticle

Abstract

Background: Herpes zoster is a disease caused by reactivation of varicella-zoster virus in sensory cranial nerves and dorsal root ganglion. Our presumption was that epidural administration of acyclovir near the viral burden could be more advantageous than intravenous (IV) administration. The cerebrospinal fluid (CSF) concentration of acyclovir after epidural administration was determined to be higher than that after IV administration in rats. Objective: In this study, we tested the hypothesis that the concentration of acyclovir in CSF after epidural administration is higher than that achieved after IV administration in rats. Study Design: A randomized controlled animal trial. Methods: A total of 30 adult male Sprague-Dawley rats were used. The rats were randomly divided into 2 equal groups, epidural (Group Epi) and IV (Group IV) administration groups (n = 15). Group Epi was further subdivided into 3 groups according to acyclovir dosage; each group comprised 5 animals receiving injections at dosages of 0.3 mg, 0.6 mg, and 0.9 mg. Group IV was also subdivided into 3 groups receiving dosages of 3 mg, 6 mg, and 9 mg. We measured CSF and plasma acyclovir concentrations one hour after administration. Results: In Group Epi, the median plasma concentrations of acyclovir were lower than that in CSF (P < 0.05). In Group IV, the median plasma concentrations of acyclovir were significantly higher than that in CSF (P < 0.05). The CSF concentrations of acyclovir in Group Epi were significantly higher than that in Group IV (P < 0.05). The plasma concentrations of acyclovir in Group Epi were significantly lower than that in Group IV (P < 0.05). Limitations: There were no references of equivalent dosages of acyclovir between IV and epidural administration. However, it is obvious in this study that epidural administration of a low dose of acyclovir can more effectively increase its concentration in the intrathecal space than IV administration. Conclusions: Epidural administration of acyclovir provides superior drug concentrations in the intrathecal space compared to IV administration.

Original languageEnglish
Pages (from-to)E613-E619
JournalPain Physician
Volume19
Issue number4
Publication statusPublished - 2016 May 1

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Acyclovir
Intravenous Administration
Cerebrospinal Fluid
Human Herpesvirus 3
Cranial Nerves
Herpes Zoster
Spinal Ganglia
Viral Load
Sprague Dawley Rats
Randomized Controlled Trials

Keywords

  • Acyclovir
  • Epidural injection
  • Herpes zoster
  • Varicella zoster virus

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

Comparison of intrathecal concentrations of acyclovir following epidural and intravenous administration in rats. / Kim, Jae Hun; Lee, Mi Kyoung; Kim, Jung Eun; Kim, Se Hee; Choi, Sang Sik.

In: Pain Physician, Vol. 19, No. 4, 01.05.2016, p. E613-E619.

Research output: Contribution to journalArticle

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abstract = "Background: Herpes zoster is a disease caused by reactivation of varicella-zoster virus in sensory cranial nerves and dorsal root ganglion. Our presumption was that epidural administration of acyclovir near the viral burden could be more advantageous than intravenous (IV) administration. The cerebrospinal fluid (CSF) concentration of acyclovir after epidural administration was determined to be higher than that after IV administration in rats. Objective: In this study, we tested the hypothesis that the concentration of acyclovir in CSF after epidural administration is higher than that achieved after IV administration in rats. Study Design: A randomized controlled animal trial. Methods: A total of 30 adult male Sprague-Dawley rats were used. The rats were randomly divided into 2 equal groups, epidural (Group Epi) and IV (Group IV) administration groups (n = 15). Group Epi was further subdivided into 3 groups according to acyclovir dosage; each group comprised 5 animals receiving injections at dosages of 0.3 mg, 0.6 mg, and 0.9 mg. Group IV was also subdivided into 3 groups receiving dosages of 3 mg, 6 mg, and 9 mg. We measured CSF and plasma acyclovir concentrations one hour after administration. Results: In Group Epi, the median plasma concentrations of acyclovir were lower than that in CSF (P < 0.05). In Group IV, the median plasma concentrations of acyclovir were significantly higher than that in CSF (P < 0.05). The CSF concentrations of acyclovir in Group Epi were significantly higher than that in Group IV (P < 0.05). The plasma concentrations of acyclovir in Group Epi were significantly lower than that in Group IV (P < 0.05). Limitations: There were no references of equivalent dosages of acyclovir between IV and epidural administration. However, it is obvious in this study that epidural administration of a low dose of acyclovir can more effectively increase its concentration in the intrathecal space than IV administration. Conclusions: Epidural administration of acyclovir provides superior drug concentrations in the intrathecal space compared to IV administration.",
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N2 - Background: Herpes zoster is a disease caused by reactivation of varicella-zoster virus in sensory cranial nerves and dorsal root ganglion. Our presumption was that epidural administration of acyclovir near the viral burden could be more advantageous than intravenous (IV) administration. The cerebrospinal fluid (CSF) concentration of acyclovir after epidural administration was determined to be higher than that after IV administration in rats. Objective: In this study, we tested the hypothesis that the concentration of acyclovir in CSF after epidural administration is higher than that achieved after IV administration in rats. Study Design: A randomized controlled animal trial. Methods: A total of 30 adult male Sprague-Dawley rats were used. The rats were randomly divided into 2 equal groups, epidural (Group Epi) and IV (Group IV) administration groups (n = 15). Group Epi was further subdivided into 3 groups according to acyclovir dosage; each group comprised 5 animals receiving injections at dosages of 0.3 mg, 0.6 mg, and 0.9 mg. Group IV was also subdivided into 3 groups receiving dosages of 3 mg, 6 mg, and 9 mg. We measured CSF and plasma acyclovir concentrations one hour after administration. Results: In Group Epi, the median plasma concentrations of acyclovir were lower than that in CSF (P < 0.05). In Group IV, the median plasma concentrations of acyclovir were significantly higher than that in CSF (P < 0.05). The CSF concentrations of acyclovir in Group Epi were significantly higher than that in Group IV (P < 0.05). The plasma concentrations of acyclovir in Group Epi were significantly lower than that in Group IV (P < 0.05). Limitations: There were no references of equivalent dosages of acyclovir between IV and epidural administration. However, it is obvious in this study that epidural administration of a low dose of acyclovir can more effectively increase its concentration in the intrathecal space than IV administration. Conclusions: Epidural administration of acyclovir provides superior drug concentrations in the intrathecal space compared to IV administration.

AB - Background: Herpes zoster is a disease caused by reactivation of varicella-zoster virus in sensory cranial nerves and dorsal root ganglion. Our presumption was that epidural administration of acyclovir near the viral burden could be more advantageous than intravenous (IV) administration. The cerebrospinal fluid (CSF) concentration of acyclovir after epidural administration was determined to be higher than that after IV administration in rats. Objective: In this study, we tested the hypothesis that the concentration of acyclovir in CSF after epidural administration is higher than that achieved after IV administration in rats. Study Design: A randomized controlled animal trial. Methods: A total of 30 adult male Sprague-Dawley rats were used. The rats were randomly divided into 2 equal groups, epidural (Group Epi) and IV (Group IV) administration groups (n = 15). Group Epi was further subdivided into 3 groups according to acyclovir dosage; each group comprised 5 animals receiving injections at dosages of 0.3 mg, 0.6 mg, and 0.9 mg. Group IV was also subdivided into 3 groups receiving dosages of 3 mg, 6 mg, and 9 mg. We measured CSF and plasma acyclovir concentrations one hour after administration. Results: In Group Epi, the median plasma concentrations of acyclovir were lower than that in CSF (P < 0.05). In Group IV, the median plasma concentrations of acyclovir were significantly higher than that in CSF (P < 0.05). The CSF concentrations of acyclovir in Group Epi were significantly higher than that in Group IV (P < 0.05). The plasma concentrations of acyclovir in Group Epi were significantly lower than that in Group IV (P < 0.05). Limitations: There were no references of equivalent dosages of acyclovir between IV and epidural administration. However, it is obvious in this study that epidural administration of a low dose of acyclovir can more effectively increase its concentration in the intrathecal space than IV administration. Conclusions: Epidural administration of acyclovir provides superior drug concentrations in the intrathecal space compared to IV administration.

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