Faglige interesser
Jeg er nysgjerrig på mekanismene som ligger til grunn for inter-individuell variasjon i farmakokinetikk.
For å forske på dette tar vi i bruk verktøy som populasjons- og fysiologi-baserte farmakokinetiske modeller. I tillegg benytter vi kliniske studier og in vitro - in vivo ekstrapolering.
Undervisning
Verv
Bakgrunn
Master i Farmasi, Farmasøytisk Institutt, Universitetet i Oslo, 2019
Developing a method to measure tacrolimus-induced tremor in kidney-transplant recipients
Emneord:
Farmakokinetikk,
Legemiddelmetabolisme,
Legemiddeltransport,
In-vitro in-vivo ekstrapolering,
Fysiologibasert farmakokinetisk modellering
Publikasjoner
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Hovd, Markus Herberg; Robertsen, Ida; Woillard, Jean-Baptiste & Åsberg, Anders
(2023).
A Method for Evaluating Robustness of Limited Sampling Strategies—Exemplified by Serum Iohexol Clearance for Determination of Measured Glomerular Filtration Rate.
Pharmaceutics.
ISSN 1999-4923.
15(4).
doi:
10.3390/pharmaceutics15041073.
Fulltekst i vitenarkiv
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Hovd, Markus Herberg; Mariussen, Espen; Uggerud, Hilde Thelle; Lashkarivand, Aslan; Christensen, Hege & Ringstad, Geir
[Vis alle 7 forfattere av denne artikkelen]
(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.
doi:
10.1186/s12987-022-00352-w.
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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.
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Kvitne, Kine Eide; Krogstad, Veronica; Wegler, Christine; Johnson, Line Kristin; Kringen, Marianne K. & Hovd, Markus Herberg
[Vis alle 19 forfattere av denne artikkelen]
(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),
s. 4121–4133.
doi:
10.1111/bcp.15349.
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Roux-en-Y gastric bypass (RYGB) may influence drug disposition due to surgery-induced gastrointestinal alterations and/or subsequent weight loss. The objective was to compare short- and long-term effects of RYGB and diet on the metabolic ratios of paraxanthine/caffeine (cytochrome P450 [CYP] 1A2 activity), 5-hydroxyomeprazole/omeprazole (CYP2C19 activity) and losartan/losartan carboxylic acid (CYP2C9 activity), and cross-sectionally compare these CYP-activities with normal-to-overweight controls.
Methods
This trial included patients with severe obesity preparing for RYGB (n = 40) or diet-induced (n = 41) weight loss, and controls (n = 18). Both weight loss groups underwent a 3-week low-energy diet (<1200 kcal/day, weeks 0-3) followed by a 6-week very-low-energy diet or RYGB (both <800 kcal/day, weeks 3-9). Follow-up time was 2 years, with four pharmacokinetic investigations.
Results
Mean ± SD weight loss from baseline was similar in the RYGB-group (13 ± 2.4%) and the diet group (10.5 ± 3.9%) at week 9, but differed at year 2 (RYGB −30 ± 6.9%, diet −3.1 ± 6.3%). From weeks 0 to 3, mean (95% confidence interval [CI]) CYP2C19 activity similarly increased in both groups (RYGB 43% [16, 55], diet 48% [22, 60]). Mean CYP2C19 activity increased by 30% (2.6, 43) after RYGB (weeks 3-9), but not in the diet-group (between-group difference −0.30 [−0.63, 0.03]). CYP2C19 activity remained elevated in the RYGB group at year 2. Baseline CYP2C19 activity was 2.7-fold higher in controls compared with patients with obesity, whereas no difference was observed in CYP1A2 and CYP2C9 activities.
Conclusion
Our findings suggest that CYP2C19 activity is lower in patients with obesity and increases following weight loss. This may be clinically relevant for drug dosing. No clinically significant effect on CYP1A2 and CYP2C9 activities was observed.
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Se alle arbeider i Cristin
Publisert
12. aug. 2019 10:17
- Sist endret
17. feb. 2023 21:54