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In vitro evidence f...
In vitro evidence for auto-induction of artemisinin metabolism in the rat.
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Gupta, S (författare)
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Svensson, U S (författare)
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- Ashton, Michael, 1955 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för fysiologi och farmakologi, Avdelningen för farmakologi,Institute of Physiology and Pharmacology, Dept of Pharmacology
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(creator_code:org_t)
- 2001
- 2001
- Engelska.
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Ingår i: European journal of drug metabolism and pharmacokinetics. - 0378-7966. ; 26:3, s. 173-8
- Relaterad länk:
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https://gup.ub.gu.se...
Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Nyckelord
- 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
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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