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| 2. |
- Jansson, Rasmus, et al.
(författare)
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Enantioselective and dose dependent intestinal absorption of eflornithine in the rat
- 2008
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Ingår i: Antimicrobial Agents and Chemotherapy. - 0066-4804 .- 1098-6596. ; 52:8, s. 2842-2848
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Tidskriftsartikel (refereegranskat)abstract
- This study aimed to investigate if the absorption of the human African trypanosomiasis agent eflornithine was stereospecific and dose dependent after oral administration. Male Sprague-Dawley rats were administered single doses of racemic eflornithine hydrochloride as an oral solution (750, 1,500, 2,000, or 3,000 mg/kg of body weight) or intravenously (375 or 1,000 mg/kg of body weight). Sparse blood samples were obtained for determination of eflornithine enantiomers by liquid chromatography with evaporative light-scattering detection (lower limit of quantification [LLOQ], 83 microM for 300 microl plasma). The full plasma concentration-time profile of racemic eflornithine following frequent sampling was determined for another group of rats, using a high-performance liquid chromatography-UV method (LLOQ, 5 microM for 50 microl plasma). Pharmacokinetic data were analyzed in NONMEM for the combined racemic and enantiomeric concentrations. Upon intravenous administration, the plasma concentration-time profile of eflornithine was biphasic, with marginal differences in enantiomer kinetics (mean clearances of 14.5 and 12.6 ml/min/kg for L- and D-eflornithine, respectively). The complex absorption kinetics were modeled with a number of transit compartments to account for delayed absorption, transferring the drug into an absorption compartment from which the rate of influx was saturable. The mean bioavailabilities for L- and D-eflornithine were 41% and 62%, respectively, in the dose range of 750 to 2,000 mg/kg of body weight, with suggested increases to 47% and 83%, respectively, after a dose of 3,000 mg/kg of body weight. Eflornithine exhibited enantioselective absorption, with the more potent L-isomer being less favored, a finding which may help to explain why clinical attempts to develop an oral treatment have hitherto failed. The mechanistic explanation for the stereoselective absorption remains unclear.
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| 3. |
- Jansson, Rasmus, 1979, et al.
(författare)
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Enantioselective and nonlinear intestinal absorption of eflornithine in the rat.
- 2008
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Ingår i: Antimicrobial Agents and Chemotherapy. - 0066-4804 .- 1098-6596. ; 52:8, s. 2842-8
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Tidskriftsartikel (refereegranskat)abstract
- This study aimed to investigate if the absorption of the human African trypanosomiasis agent eflornithine was stereospecific and dose dependent after oral administration. Male Sprague-Dawley rats were administered single doses of racemic eflornithine hydrochloride as an oral solution (750, 1,500, 2,000, or 3,000 mg/kg of body weight) or intravenously (375 or 1,000 mg/kg of body weight). Sparse blood samples were obtained for determination of eflornithine enantiomers by liquid chromatography with evaporative light-scattering detection (lower limit of quantification [LLOQ], 83 M for 300 l plasma). The full plasma concentration-time profile of racemic eflornithine following frequent sampling was determined for another group of rats, using a high-performance liquid chromatography–UV method (LLOQ, 5 M for 50 l plasma). Pharmacokinetic data were analyzed in NONMEM for the combined racemic and enantiomeric concentrations. Upon intravenous administration, the plasma concentration-time profile of eflornithine was biphasic, with marginal differences in enantiomer kinetics (mean clearances of 14.5 and 12.6 ml/min/kg for L- and D-eflornithine, respectively). The complex absorption kinetics were modeled with a number of transit compartments to account for delayed absorption, transferring the drug into an absorption compartment from which the rate of influx was saturable. The mean bioavailabilities for L- and D-eflornithine were 41% and 62%, respectively, in the dose range of 750 to 2,000 mg/kg of body weight, with suggested increases to 47% and 83%, respectively, after a dose of 3,000 mg/kg of body weight. Eflornithine exhibited enantioselective absorption, with the more potent L-isomer being less favored, a finding which may help to explain why clinical attempts to develop an oral treatment have hitherto failed. The mechanistic explanation for the stereoselective absorption remains unclear.
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| 6. |
- Lindkvist, Jenny, et al.
(författare)
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Straightforward and rapid determination of sulfadoxine and sulfamethoxazole in capillary blood on sampling paper with liquid chromatography and UV detection
- 2009
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Ingår i: Transactions of the Royal Society of Tropical Medicine and Hygiene. - : Oxford University Press (OUP). - 0035-9203 .- 1878-3503. ; 103:4, s. 371-376
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Tidskriftsartikel (refereegranskat)abstract
- A method for the determination of sulfadoxine and sulfamethoxazole in capillary blood on sampling paper has been developed and validated. The method is straightforward with minimal sample preparation, and is suitable for rural settings. Separation of sulfadoxine, sulfamethoxazole and internal standard was performed using a Purospher STAR RP-18 endcapped LC column (150×4.6mm) with a mobile phase consisting of acetonitrile:sodium acetate buffer pH 5.2, I=0.1 (1:2, v/v). For sulfadoxine, the within-day precision was 5.3% at 15μmol/l and 3.7% at 600μmol/l, while for sulfamethoxazole it was 5.7% at 15μmol/l and 3.8% at 600μmol/l. The lower limit of quantification was determined to 5μmol/l and precision was 5.5% and 5.0% for sulfadoxine and sulfamethoxazole, respectively.
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| 9. |
- Malm, Mikaela, et al.
(författare)
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Automated solid-phase extraction method for the determination of piperaquine in capillary blood applied onto sampling paper by liquid chromatography
- 2004
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Ingår i: Journal of Chromatography B. ; :809, s. 43-49
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Tidskriftsartikel (refereegranskat)abstract
- A bioanalytical method for the determination of piperaquine in 100 uL blood applied onto sampling paper, by solid-phase extraction and liquid chromatography, has been developed and validated. Blood spots were cut into small pieces prior to addition of 0.3 M perchloric acid, acetonitrile and phosphate buffer containing an internal standard. The liquid phase was loaded onto a mixed phase cation-exchange (MPC) solid-phase extraction column. Piperaquine and the internal standard were analysed by liquid chromatography and separated on a Chromolith Performance (100 mm x 4.6 mm) column with acetonitrile: phosphate buffer pH 2.5, I = 0.1 (8:92, v/v) at the flow of 3.5 mL/min. The UV detection was performed at 345 nm. the intra-assay precision was 12.0% at 0.150 uM, 7.3% at 1.25 uM and 7.3% at 2.25 uM. The inter-assay precison was 1.8% at 0.150 uM, 5.2% at 1.25 uM and 2.8% at 2.25 uM. The lower limit of quantification (LLOQ) was determined to 0.050 uM where the precison was 14.7%.
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