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- Asimus, Sara, 1976, et al.
(författare)
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Artemisinin antimalarials moderately affect cytochrome P450 enzyme activity in healthy subjects.
- 2007
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Ingår i: Fundamental & Clinical Pharmacology. - : Wiley. - 0767-3981 .- 1472-8206. ; 21:3, s. 307-316
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate which principal human cytochrome P450 (CYP450) enzymes are affected by artemisinin and to what degree the artemisinin derivatives differ with respect to their respective induction and inhibition capacity. Seventy-five healthy adults were randomized to receive therapeutic oral doses of artemisinin, dihydroartemisinin, arteether, artemether or artesunate for 5 days (days 1–5). A six-drug cocktail consisting of caffeine, coumarin, mephenytoin, metoprolol, chlorzoxazone and midazolam was administered orally on days −6, 1, 5 and 10 to assess the activities of CYP1A2, CYP2A6, CYP2C19, CYP2D6, CYP2E1 and CYP3A, respectively. Four-hour plasma concentrations of parent drugs and corresponding metabolites and 7-hydroxycoumarin urine concentrations were quantified by liquid chromatography-tandem mass spectrometry. The 1-hydroxymidazolam/midazolam 4-h plasma concentration ratio (CYP3A) was increased on day 5 by artemisinin [2.66-fold (98.75% CI: 2.10–3.36)], artemether [1.54 (1.14–2.09)] and dihydroartemisinin [1.25 (1.06–1.47)] compared with day −6. The S-4'-hydroxymephenytoin/S-mephenytoin ratio (CYP2C19) was increased on day 5 by artemisinin [1.69 (1.47–1.94)] and arteether [1.33 (1.15–1.55)] compared with day −6. The paraxanthine/caffeine ratio (CYP1A2) was decreased on day 1 after administration of artemisinin [0.27 (0.18–0.39)], arteether [0.70 (0.55–0.89)] and dihydroartemisinin [0.73 (0.59–0.90)] compared with day −6. The α-hydroxymetoprolol/metoprolol ratio (CYP2D6) was lower on day 1 compared with day −6 in the artemisinin [0.82 (0.70–0.96)] and dihydroartemisinin [0.83 (0.71–0.96)] groups, respectively. In the artemisinin-treated subjects this decrease was followed by a 1.34-fold (1.14–1.58) increase from day 1 to day 5. These results show that intake of artemisinin antimalarials affect the activities of several principal human drug metabolizing CYP450 enzymes. Even though not significant in all treatment groups, changes in the individual metrics were of the same direction for all the artemisinin drugs, suggesting a class effect that needs to be considered in the development of new artemisinin derivatives and combination treatments of malaria.
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2. |
- Bergman, Eva, et al.
(författare)
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Self-administered measurement of symphysis-fundus heights
- 2007
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 86:6, s. 671-677
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Tidskriftsartikel (refereegranskat)abstract
- Background. Antenatal identification of infants small for gestational age (SGA) improves their perinatal outcome. Repeated measurements of the symphysis-fundus (SF) heights performed by midwives is the most widespread screening method for detection of SGA. However the insufficiency of this method necessitates improved practices. Earlier start and more frequent SF measurements, which could be acomplished by self-administered measurements, might improve the ability to detect deviant growth. The present study was set up to evaluate wether pregnant wome can reliable perform SF measurements by themself. Method. Forty healthy women with singelton and ultrasound-dated pregancies from 2 antenatal clinics in Uppsala, Sweden, were asked to perform 4 consecutive SF measureemnts once a week, from 20 to 25 weeks of gestation until delivery. The self-administered SF measurements were recorded and systematically compared with midwives' SF measurements. Results. Thirty-three pregnant women performed self-administered SF measurements over a 14-week period (range 1-21). The SF curves constructed from self-admiinistered SF measurements had the same shape as previously constructed population-based reference curves. The variance for self-admiinistered SF measurements was higher than that of the midwives. Conclusions. Pregnant women are capable of measuring SF heights by themselves, but with a higher individual variance than midwives. Repeated measurements at each occasion can compensate for the higher variance. The main advantage of self-administered SF measurements is the opportunity to follow fetal growth earlier and more frequently.
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