id:"swepub:oai:DiVA.org:uu-103241"
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| Fältnamn | Indikatorer | Metadata |
|---|---|---|
| 000 | 04754naa a2200505 4500 | |
| 001 | oai:DiVA.org:uu-103241 | |
| 003 | SwePub | |
| 008 | 090515s2006 | |||||||||||000 ||eng| | |
| 024 | 7 | a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-1032412 URI |
| 024 | 7 | a https://doi.org/10.1007/s10928-005-9001-12 DOI |
| 040 | a (SwePub)uu | |
| 041 | a engb eng | |
| 042 | 9 SwePub | |
| 072 | 7 | a ref2 swepub-contenttype |
| 072 | 7 | a art2 swepub-publicationtype |
| 100 | 1 | a Bergström, Matsu Uppsala universitet,Institutionen för farmaceutisk biovetenskap4 aut |
| 245 | 1 0 | a Blood-brain barrier penetration of zolmitriptan--modelling of positron emission tomography data |
| 264 | c 2006-01-10 | |
| 264 | 1 | b Springer Science and Business Media LLC,c 2006 |
| 338 | a print2 rdacarrier | |
| 520 | a Positron emission tomography (PET) with the drug radiolabelled allows a direct measurement of brain or other organ kinetics, information which can be essential in drug development. Usually, however, a PET-tracer is administered intravenously (i.v.), whereas the therapeutic drug is mostly given orally or by a different route to the PET-tracer. In such cases, a recalculation is needed to make the PET data representative for the alternative administration route. To investigate the blood-brain barrier penetration of a drug (zolmitriptan) using dynamic PET and by PK modelling quantify the brain concentration of the drug after the nasal administration of a therapeutic dose. [11C]Zolmitriptan at tracer dose was administered as a short i.v. infusion and the brain tissue and venous blood kinetics of [11C]zolmitriptan was measured by PET in 7 healthy volunteers. One PET study was performed before and one 30 min after the administration of 5 mg zolmitriptan as nasal spray. At each of the instances, the brain radioactivity concentration after subtraction of the vascular component was determined up to 90 min after administration and compared to venous plasma radioactivity concentration after correction for radiolabelled metabolites. Convolution methods were used to describe the relationship between arterial and venous tracer concentrations, respectively between brain and arterial tracer concentration. Finally, the impulse response functions derived from the PET studies were applied on plasma PK data to estimate the brain zolmitriptan concentration after a nasal administration of a therapeutic dose. The studies shows that the PET data on brain kinetics could well be described as the convolution of venous tracer kinetics with an impulse response including terms for arterial-to-venous plasma and arterial-to-brain impulse responses. Application of the PET derived impulse responses on the plasma PK from nasal administration demonstrated that brain PK of zolmitriptan increased with time, achieving about 0.5 mg/ml at 30 min and close to a maximum of 1.5 mg/ml after 2 hr. A significant brain concentration was observed already after 5 min. The data support the notation of a rapid brain availability of zolmitriptan after nasal administration. | |
| 650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Farmaceutiska vetenskaper0 (SwePub)301012 hsv//swe |
| 650 | 7 | a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Pharmaceutical Sciences0 (SwePub)301012 hsv//eng |
| 653 | a Blood-Brain Barrier/*metabolism/*radionuclide imaging | |
| 653 | a Carbon Radioisotopes | |
| 653 | a Female | |
| 653 | a Humans | |
| 653 | a Male | |
| 653 | a Models; Biological | |
| 653 | a Oxazolidinones/blood/*pharmacokinetics | |
| 653 | a Positron-Emission Tomography | |
| 653 | a Serotonin Agonists/blood/*pharmacokinetics | |
| 653 | a Tissue Distribution | |
| 653 | a Tryptamines/blood/*pharmacokinetics | |
| 653 | a PHARMACY | |
| 653 | a FARMACI | |
| 700 | 1 | a Yates, Roger4 aut |
| 700 | 1 | a Wall, Andersu Uppsala universitet,Institutionen för onkologi, radiologi och klinisk immunologi4 aut |
| 700 | 1 | a Kågedal, Mattsu Uppsala universitet,Avdelningen för farmakokinetik och läkemedelsterapi,Karlsson4 aut0 (Swepub:uu)matka828 |
| 700 | 1 | a Syvänen, Stinau Uppsala universitet,Avdelningen för farmakokinetik och läkemedelsterapi,Hammarlund-Udenaes4 aut0 (Swepub:uu)stsyv838 |
| 700 | 1 | a Långström, Bengtu Uppsala universitet,Institutionen för biokemi och organisk kemi4 aut0 (Swepub:uu)benglang |
| 710 | 2 | a Uppsala universitetb Institutionen för farmaceutisk biovetenskap4 org |
| 773 | 0 | t Journal of Pharmacokinetics and Pharmacodynamicsd : Springer Science and Business Media LLCg 33:1, s. 75-91q 33:1<75-91x 1567-567Xx 1573-8744 |
| 856 | 4 8 | u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-103241 |
| 856 | 4 8 | u https://doi.org/10.1007/s10928-005-9001-1 |
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