Markus Herberg Hovd

• Hovd, Markus Herberg; Mariussen, Espen; Uggerud, Hilde Thelle; Lashkarivand, Aslan; Christensen, Hege & Ringstad, Geir [Show all 7 contributors for this article] (2022). Population pharmacokinetic modeling of CSF to blood clearance: prospective tracer study of 161 patients under work-up for CSF disorders. Fluids and Barriers of the CNS. ISSN 2045-8118. 19(1). doi: 10.1186/s12987-022-00352-w. Full text in Research Archive Show summary

  Background Quantitative measurements of cerebrospinal fluid to blood clearance has previously not been established for neurological diseases. Possibly, variability in cerebrospinal fluid clearance may affect the underlying disease process and may possibly be a source of under- or over-dosage of intrathecally administered drugs. The aim of this study was to characterize the cerebrospinal fluid to blood clearance of the intrathecally administered magnetic resonance imaging contrast agent gadobutrol (Gadovist, Bayer Pharma AG, GE). For this, we established a population pharmacokinetic model, hypothesizing that cerebrospinal fluid to blood clearance differs between cerebrospinal fluid diseases. Methods Gadobutrol served as a surrogate tracer for extra-vascular pathways taken by several brain metabolites and drugs in cerebrospinal fluid. We estimated cerebrospinal fluid to blood clearance in patients with different cerebrospinal fluid disorders, i.e. symptomatic pineal and arachnoid cysts, as well as tentative spontaneous intracranial hypotension due to cerebrospinal fluid leakage, idiopathic intracranial hypertension, or different types of hydrocephalus (idiopathic normal pressure hydrocephalus, communicating- and non-communicating hydrocephalus). Individuals with no verified cerebrospinal fluid disturbance at clinical work-up were denoted references. Results Population pharmacokinetic modelling based on 1,140 blood samples from 161 individuals revealed marked inter-individual variability in pharmacokinetic profiles, including differences in absorption half-life (time to 50% of tracer absorbed from cerebrospinal fluid to blood), time to maximum concentration in blood and the maximum concentration in blood as well as the area under the plasma concentration time curve from zero to infinity. In addition, the different disease categories of cerebrospinal fluid diseases demonstrated different profiles. Conclusions The present observations of considerable variation in cerebrospinal fluid to blood clearance between individuals in general and across neurological diseases, may suggest that defining cerebrospinal fluid to blood clearance can become a useful diagnostic adjunct for work-up of cerebrospinal fluid disorders. We also suggest that it may become useful for assessing clearance capacity of endogenous brain metabolites from cerebrospinal fluid, as well as measuring individual cerebrospinal fluid to blood clearance of intrathecal drugs.

• Kvitne, Kine Eide; Krogstad, Veronica; Wegler, Christine; Johnson, Line Kristin; Kringen, Marianne K. & Hovd, Markus Herberg [Show all 19 contributors for this article] (2022). Short- and long-term effects of body weight, calorie restriction and gastric bypass on CYP1A2, CYP2C19 and CYP2C9 activity. British Journal of Clinical Pharmacology. ISSN 0306-5251. 88(9), p. 4121–4133. doi: 10.1111/bcp.15349. Full text in Research Archive
• Eide, Per Kristian; Mariussen, Espen; Uggerud, Hilde Thelle; Pripp, Are Hugo; Lashkarivand, Aslan & Hassel, Bjørnar [Show all 8 contributors for this article] (2021). Clinical application of intrathecal gadobutrol for assessment of cerebrospinal fluid tracer clearance to blood. JCI Insight. ISSN 2379-3708. 6(9), p. 1–13. doi: 10.1172/jci.insight.147063. Full text in Research Archive

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