Till sidans topp

Sidansvarig: Webbredaktion
Sidan uppdaterades: 2012-09-11 15:12

Tipsa en vän
Utskriftsversion

In vitro evidence for aut… - Göteborgs universitet Till startsida
Webbkarta
Till innehåll Läs mer om hur kakor används på gu.se

In vitro evidence for auto-induction of artemisinin metabolism in the rat.

Artikel i vetenskaplig tidskrift
Författare S Gupta
U S Svensson
Michael Ashton
Publicerad i European journal of drug metabolism and pharmacokinetics
Volym 26
Nummer/häfte 3
Sidor 173-8
ISSN 0378-7966
Publiceringsår 2001
Publicerad vid Institutionen för fysiologi och farmakologi, Avdelningen för farmakologi
Sidor 173-8
Språk en
Länkar www.ncbi.nlm.nih.gov/entrez/query.f...
Ämnesord Animals, Antimalarials, pharmacokinetics, pharmacology, Artemisinins, Biotransformation, drug effects, Chromatography, High Pressure Liquid, Male, Microsomes, Liver, metabolism, Rats, Rats, Sprague-Dawley, Sesquiterpenes, pharmacokinetics, pharmacology, Spectrophotometry, Ultraviolet
Ämneskategorier Biofarmaci

Sammanfattning

Artemisinin disappearance rate was more rapid in incubations with liver microsomes from rats pre-treated with oral artemisinin (60 mg/kg/day for 5 days) compared with microsomes from control animals. A single pathway Michaelis-Menten saturable elimination model was fitted to the concentration-time data of artemisinin incubations by non-linear regression. Model parameters were obtained after fitting results for each animal separately and by pooling data for pre-treated and control animals. Parameter estimates (% coefficient of variation) from fitting the pooled data was maximum velocities (Vmax) = 1.8 (12) mmole/min/mg protein and Michaelis constants (Km) = 20(22) microM for artemisinin pre-treated and Vmax = 0.85 (35) mmole/min/mg protein and Km = 67(52) microM for control animals indicating a 2-fold increase in Vmax and a 3-fold decrease in Km with microsomes from artemisinin pre-treated animals. Estimates of intrinsic clearance in microsomes from the pre-treated animals were 8-fold higher compared with controls. Thus, artemisinin appears to be a potent auto-inducer of drug metabolism in rats as has also been observed in humans. The present findings suggest caution in the interpretation of repeat-dose rat toxicity studies with artemisinin unless its pharmacokinetics are simultaneously monitored, since during multiple administration, the exposure of the drug will not be constant over time.

Sidansvarig: Webbredaktion|Sidan uppdaterades: 2012-09-11
Dela:

På Göteborgs universitet använder vi kakor (cookies) för att webbplatsen ska fungera på ett bra sätt för dig. Genom att surfa vidare godkänner du att vi använder kakor.  Vad är kakor?

Denna text är utskriven från följande webbsida:
http://gu.se/forskning/publikation/?languageId=100000&disableRedirect=true&returnUrl=http%3A%2F%2Fgu.se%2Fenglish%2Fresearch%2Fpublication%2F%3FlanguageId%3D100001%26publicationId%3D186719&publicationId=186719
Utskriftsdatum: 2020-08-12