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Göteborgs universitets publikationer

Population pharmacokinetics of artesunate and dihydroartemisinin during long-term oral administration of artesunate to patients with metastatic breast cancer.

Författare och institution:
Therese Ericsson (Institutionen för neurovetenskap och fysiologi, sektionen för farmakologi); Antje Blank (-); Cornelia von Hagens (-); Michael Ashton (Institutionen för neurovetenskap och fysiologi, sektionen för farmakologi); Angela Abelö (Institutionen för neurovetenskap och fysiologi, sektionen för farmakologi)
Publicerad i:
European Journal of Clinical Pharmacology, 70 ( 12 ) s. 1453-63
Artikel, refereegranskad vetenskaplig
Sammanfattning (abstract):
PURPOSE: The purpose of this study were firstly to characterize the population pharmacokinetics of artesunate (ARS) and its active metabolite dihydroartemisinin (DHA) in patients with metastatic breast cancer during long-term (>3 weeks) daily oral ARS administration and secondly to study the relationship between salivary and plasma concentrations of DHA. METHODS: Drug concentration-time data from 23 patients, receiving oral ARS (100, 150, or 200 mg OD), was analyzed using nonlinear mixed effects modeling. A combined drug-metabolite population pharmacokinetic model was developed to describe the plasma pharmacokinetics of ARS and DHA in plasma. Saliva drug concentrations were incorporated as being directly proportional to plasma concentrations. RESULTS: A first-order absorption model for ARS linked to a combined two-compartment disposition model for ARS and one-compartment disposition model for DHA provided the best fit to the data. No covariates were identified that could explain between-subject variability. A time-dependent increase in apparent elimination clearance of DHA was observed. Salivary DHA concentrations were proportionally correlated with total DHA plasma concentrations, with an estimated slope factor of 0.116. CONCLUSIONS: Population pharmacokinetics of ARS and DHA in patients with breast cancer was well described by a combined drug-metabolite model without any covariates and with an increase in apparent elimination clearance of DHA over time. The estimated DHA saliva/plasma ratio was in good agreement with the reported DHA unbound fraction in human plasma. Saliva ARS concentrations correlated poorly with plasma concentrations. This suggests the use of saliva sampling for therapeutic drug monitoring of DHA. However, further studies are warranted to investigate the robustness of this approach.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
Medicinska grundvetenskaper ->
Farmakologi och toxikologi ->
Klinisk farmakologi
Klinisk medicin ->
Cancer och onkologi
Postens nummer:
Posten skapad:
2014-11-21 08:31
Posten ändrad:
2014-11-26 14:53

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