Till sidans topp

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

Tipsa en vän
Utskriftsversion

Enantiospecific Reassessm… - Göteborgs universitet Till startsida
Webbkarta
Till innehåll Läs mer om hur kakor används på gu.se

Enantiospecific Reassessment of the Pharmacokinetics and Pharmacodynamics of Oral Eflornithine against Late-Stage Trypanosoma brucei gambiense Sleeping Sickness

Artikel i vetenskaplig tidskrift
Författare Rasmus Jansson Löfmark
K. Na-Bangchang
S. Bjorkman
F. Doua
Michael Ashton
Publicerad i Antimicrobial Agents and Chemotherapy
Volym 59
Nummer/häfte 2
Sidor 1299-1307
ISSN 0066-4804
Publiceringsår 2015
Publicerad vid Institutionen för neurovetenskap och fysiologi, sektionen för farmakologi
Sidor 1299-1307
Språk en
Länkar dx.doi.org/10.1128/aac.04101-14
Ämnesord HUMAN AFRICAN TRYPANOSOMIASIS, CEREBROSPINAL-FLUID, ALPHA-DIFLUOROMETHYLORNITHINE, ORNITHINE-DECARBOXYLASE, COMBINATION, THERAPY, DRUG ABSORPTION, MODEL, MELARSOPROL, ENANTIOMERS, PLASMA, Microbiology, Pharmacology & Pharmacy
Ämneskategorier Farmakologi

Sammanfattning

This study aimed to characterize the stereoselective pharmacokinetics of oral eflornithine in 25 patients with late-stage Trypanosoma brucei gambiense sleeping sickness. A secondary aim was to determine the concentrations of L-and D-eflornithine required in plasma or cerebrospinal fluid (CSF) for an efficient eradication of the T. brucei gambiense parasites. Patients were randomly allocated to receive either 100 (group I, n = 12) or 125 (group II, n = 13) mg/kg of body weight of drug every 6 h for 14 days. The concentrations of L-and D-eflornithine in the plasma and CSF samples were measured using a stereospecific liquid chromatographic method. Nonlinear mixed-effects modeling was used to characterize the plasma pharmacokinetics. The plasma concentrations of L-eflornithine were on average 52% (95% confidence interval [CI], 51, 54%; n = 321) of the D-enantiomer concentrations. The typical oral clearances of L-and D-eflornithine were 17.4 (95% CI, 15.5, 19.3) and 8.23 (95% CI, 7.36, 9.10) liters/h, respectively. These differences were likely due to stereoselective intestinal absorption. The distributions of eflornithine enantiomers to the CSF were not stereoselective. A correlation was found between the probability of cure and plasma drug exposure, although it was not more pronounced for the L-enantiomer than for that of total eflornithine. This study may explain why oral treatment for late-stage human African trypanosomiasis (HAT) patients with racemic eflornithine has previously failed; the more potent L-enantiomer is present at much lower concentrations in both plasma and CSF than those of the D-enantiomer. Eflornithine stereoselective pharmacokinetics needs to be considered if an oral dosage regimen is to be explored further.

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://www.gu.se/forskning/publikation/?publicationId=213502
Utskriftsdatum: 2019-08-19