Session Type: ePosters
Session Title: ePosters
Authors(s): T. Mariager (1), F. Sörgel (2), R. Nau (3), C.R. Bjarkam (4), H. Nielsen (1), J. Bodilsen (1)
Authors Affiliations(s): (1) Department of Infectious diseases, Aalborg University Hospital, Denmark, (2) Institute for Biomedical and Pharmaceutical Research, Germany, (3) Institute of Neuropathology, University Medical Center, Germany, (4) Department of Neurosurgery, Aalborg University Hospital, Denmark
Background:
Viral encephalitis caused by herpes simplex virus type 1 (HSV-1) or varicella-zoster virus are devastating infections with high mortality rates if untreated. Measurements on the intracellular concentrations of acyclovir in neurons is not possible in vivo and thus far, acyclovir treatment for viral encephalitis mainly relies on a limited number of pharmacokinetic analyses of acyclovir concentrations in cerebrospinal fluid (CSF). Therefore, innovative experimental models may help to improve acyclovir treatment of viral encephalitis.
Methods:This experimental pilot study aimed to develop a novel in vivo pharmacokinetic model of the intracerebral penetration of intravenous acyclovir (10 mg/kg). Specifically, continuous samplings were performed from 1) superficial cerebral cortex by microdialysis and 2) CSF in the lower spinal canal by lumbar puncture. Intracerebral extracellular fluid (ECF) concentrations of acyclovir were compared to their corresponding concentrations in CSF and plasma. For this proof-of-concept model, a single pig was monitored during a 3-hour period. Drug concentrations were determined by mass spectrophotometry with a lower quantification limit >0.109 µg/mL.
Results:Drug concentrations exceeded the detection threshold 30 min post dosage in plasma and 1 hr post dosage in CSF. Plasma concentration reached Cmax at 1hr (7.88 µg/mL) compared to a prolonged penetration observed within CSF by Cmax at 2 hr (1.58 µg/mL). Average CSF:plasma ratio was 0.475 and ranged from 0.063 (1 hr post dosage) to 0.764 (3 hr post-dose). Intracerebral ECF drug concentration analyses are scheduled for March 2021. Experiences from these preliminary analyses will form the foundation for an expanded setup during the spring of 2021. Drug concentration will be monitored within brain segments affected in viral encephalitis (superficial temporal cortex and deep cortical structures) and compared to concentration in CSF from different parts of the spinal canal during a 12-hour period.
Conclusions:Due to their physical size and genetic profile, pigs constitute a favourable pharmacokinetic model for antimicrobial treatment of CNS infections in humans. Preliminary results from this study are comparable to previous findings of plasma and CSF concentrations. Thus, this model could prove valuable for future studies of antimicrobial distribution within different compartments of the brain including the ECF.
Keyword(s): Viral Encephalitis, Pharmacokinetics, Animal modelSession Type: ePosters
Session Title: ePosters
Authors(s): T. Mariager (1), F. Sörgel (2), R. Nau (3), C.R. Bjarkam (4), H. Nielsen (1), J. Bodilsen (1)
Authors Affiliations(s): (1) Department of Infectious diseases, Aalborg University Hospital, Denmark, (2) Institute for Biomedical and Pharmaceutical Research, Germany, (3) Institute of Neuropathology, University Medical Center, Germany, (4) Department of Neurosurgery, Aalborg University Hospital, Denmark
Background:
Viral encephalitis caused by herpes simplex virus type 1 (HSV-1) or varicella-zoster virus are devastating infections with high mortality rates if untreated. Measurements on the intracellular concentrations of acyclovir in neurons is not possible in vivo and thus far, acyclovir treatment for viral encephalitis mainly relies on a limited number of pharmacokinetic analyses of acyclovir concentrations in cerebrospinal fluid (CSF). Therefore, innovative experimental models may help to improve acyclovir treatment of viral encephalitis.
Methods:This experimental pilot study aimed to develop a novel in vivo pharmacokinetic model of the intracerebral penetration of intravenous acyclovir (10 mg/kg). Specifically, continuous samplings were performed from 1) superficial cerebral cortex by microdialysis and 2) CSF in the lower spinal canal by lumbar puncture. Intracerebral extracellular fluid (ECF) concentrations of acyclovir were compared to their corresponding concentrations in CSF and plasma. For this proof-of-concept model, a single pig was monitored during a 3-hour period. Drug concentrations were determined by mass spectrophotometry with a lower quantification limit >0.109 µg/mL.
Results:Drug concentrations exceeded the detection threshold 30 min post dosage in plasma and 1 hr post dosage in CSF. Plasma concentration reached Cmax at 1hr (7.88 µg/mL) compared to a prolonged penetration observed within CSF by Cmax at 2 hr (1.58 µg/mL). Average CSF:plasma ratio was 0.475 and ranged from 0.063 (1 hr post dosage) to 0.764 (3 hr post-dose). Intracerebral ECF drug concentration analyses are scheduled for March 2021. Experiences from these preliminary analyses will form the foundation for an expanded setup during the spring of 2021. Drug concentration will be monitored within brain segments affected in viral encephalitis (superficial temporal cortex and deep cortical structures) and compared to concentration in CSF from different parts of the spinal canal during a 12-hour period.
Conclusions:Due to their physical size and genetic profile, pigs constitute a favourable pharmacokinetic model for antimicrobial treatment of CNS infections in humans. Preliminary results from this study are comparable to previous findings of plasma and CSF concentrations. Thus, this model could prove valuable for future studies of antimicrobial distribution within different compartments of the brain including the ECF.
Keyword(s): Viral Encephalitis, Pharmacokinetics, Animal model
Session Type: ePosters
Session Title: ePosters
Authors(s): T. Mariager (1), F. Sörgel (2), R. Nau (3), C.R. Bjarkam (4), H. Nielsen (1), J. Bodilsen (1)
Authors Affiliations(s): (1) Department of Infectious diseases, Aalborg University Hospital, Denmark, (2) Institute for Biomedical and Pharmaceutical Research, Germany, (3) Institute of Neuropathology, University Medical Center, Germany, (4) Department of Neurosurgery, Aalborg University Hospital, Denmark
Background:
Viral encephalitis caused by herpes simplex virus type 1 (HSV-1) or varicella-zoster virus are devastating infections with high mortality rates if untreated. Measurements on the intracellular concentrations of acyclovir in neurons is not possible in vivo and thus far, acyclovir treatment for viral encephalitis mainly relies on a limited number of pharmacokinetic analyses of acyclovir concentrations in cerebrospinal fluid (CSF). Therefore, innovative experimental models may help to improve acyclovir treatment of viral encephalitis.
Methods:This experimental pilot study aimed to develop a novel in vivo pharmacokinetic model of the intracerebral penetration of intravenous acyclovir (10 mg/kg). Specifically, continuous samplings were performed from 1) superficial cerebral cortex by microdialysis and 2) CSF in the lower spinal canal by lumbar puncture. Intracerebral extracellular fluid (ECF) concentrations of acyclovir were compared to their corresponding concentrations in CSF and plasma. For this proof-of-concept model, a single pig was monitored during a 3-hour period. Drug concentrations were determined by mass spectrophotometry with a lower quantification limit >0.109 µg/mL.
Results:Drug concentrations exceeded the detection threshold 30 min post dosage in plasma and 1 hr post dosage in CSF. Plasma concentration reached Cmax at 1hr (7.88 µg/mL) compared to a prolonged penetration observed within CSF by Cmax at 2 hr (1.58 µg/mL). Average CSF:plasma ratio was 0.475 and ranged from 0.063 (1 hr post dosage) to 0.764 (3 hr post-dose). Intracerebral ECF drug concentration analyses are scheduled for March 2021. Experiences from these preliminary analyses will form the foundation for an expanded setup during the spring of 2021. Drug concentration will be monitored within brain segments affected in viral encephalitis (superficial temporal cortex and deep cortical structures) and compared to concentration in CSF from different parts of the spinal canal during a 12-hour period.
Conclusions:Due to their physical size and genetic profile, pigs constitute a favourable pharmacokinetic model for antimicrobial treatment of CNS infections in humans. Preliminary results from this study are comparable to previous findings of plasma and CSF concentrations. Thus, this model could prove valuable for future studies of antimicrobial distribution within different compartments of the brain including the ECF.
Keyword(s): Viral Encephalitis, Pharmacokinetics, Animal modelSession Type: ePosters
Session Title: ePosters
Authors(s): T. Mariager (1), F. Sörgel (2), R. Nau (3), C.R. Bjarkam (4), H. Nielsen (1), J. Bodilsen (1)
Authors Affiliations(s): (1) Department of Infectious diseases, Aalborg University Hospital, Denmark, (2) Institute for Biomedical and Pharmaceutical Research, Germany, (3) Institute of Neuropathology, University Medical Center, Germany, (4) Department of Neurosurgery, Aalborg University Hospital, Denmark
Background:
Viral encephalitis caused by herpes simplex virus type 1 (HSV-1) or varicella-zoster virus are devastating infections with high mortality rates if untreated. Measurements on the intracellular concentrations of acyclovir in neurons is not possible in vivo and thus far, acyclovir treatment for viral encephalitis mainly relies on a limited number of pharmacokinetic analyses of acyclovir concentrations in cerebrospinal fluid (CSF). Therefore, innovative experimental models may help to improve acyclovir treatment of viral encephalitis.
Methods:This experimental pilot study aimed to develop a novel in vivo pharmacokinetic model of the intracerebral penetration of intravenous acyclovir (10 mg/kg). Specifically, continuous samplings were performed from 1) superficial cerebral cortex by microdialysis and 2) CSF in the lower spinal canal by lumbar puncture. Intracerebral extracellular fluid (ECF) concentrations of acyclovir were compared to their corresponding concentrations in CSF and plasma. For this proof-of-concept model, a single pig was monitored during a 3-hour period. Drug concentrations were determined by mass spectrophotometry with a lower quantification limit >0.109 µg/mL.
Results:Drug concentrations exceeded the detection threshold 30 min post dosage in plasma and 1 hr post dosage in CSF. Plasma concentration reached Cmax at 1hr (7.88 µg/mL) compared to a prolonged penetration observed within CSF by Cmax at 2 hr (1.58 µg/mL). Average CSF:plasma ratio was 0.475 and ranged from 0.063 (1 hr post dosage) to 0.764 (3 hr post-dose). Intracerebral ECF drug concentration analyses are scheduled for March 2021. Experiences from these preliminary analyses will form the foundation for an expanded setup during the spring of 2021. Drug concentration will be monitored within brain segments affected in viral encephalitis (superficial temporal cortex and deep cortical structures) and compared to concentration in CSF from different parts of the spinal canal during a 12-hour period.
Conclusions:Due to their physical size and genetic profile, pigs constitute a favourable pharmacokinetic model for antimicrobial treatment of CNS infections in humans. Preliminary results from this study are comparable to previous findings of plasma and CSF concentrations. Thus, this model could prove valuable for future studies of antimicrobial distribution within different compartments of the brain including the ECF.
Keyword(s): Viral Encephalitis, Pharmacokinetics, Animal model