Pharmacokinetics of Artemisinin and Artesunate after Oral Administration in Healthy Volunteers

Benakis, A.; Paris, Maria; Loutan, Louis; Plessas, Charalambos T.; Plessas, S. T.

doi:10.4269/ajtmh.1997.56.17

Cited by 98 publications

(80 citation statements)

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“…DHA has a short elimination half-life (approximately 40 min (Batty et al, 1996(Batty et al, , 1998aBenakis et al, 1997)) but little is known of its metabolism. The supposition that DHA is metabolized to inactive compounds has been supported by a recent study in which pharmacokinetic parameters for DHA were calculated from plasma concentration-time data that were obtained by bioassay (Bethell et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

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Assessment of the effect of malaria infection on hepatic clearance of dihydroartemisinin using rat liver perfusions and microsomes

Batty

Ilett

Edwards

et al. 1998

British J Pharmacology

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1 The clearance of dihydroartemisinin (DHA) in control and malaria-infected (MI) rats was investigated using the isolated perfused rat liver (IPRL) model and hepatic microsomal studies. 2 In the recirculating IPRL, clearance of DHA was reduced from a mean (s.d.) of 8.2+1.8 ml min 71 in controls (n=8) to 6.0+1.0 ml min 71 in MI (n=8; P50.01). Clearance in control livers was similar to the perfusion¯ow rate, suggesting a high hepatic extraction ratio for DHA. 3 Single-pass IPRL studies in controls (n=8) showed that DHA bioavailability at 1.3, 8 and 38 mM was 0.026+0.020, 0.043+0.025 and 0.14+0.06, respectively (P50.001 for 8 mM vs 38 mM). In MI livers (n=5), DHA bioavailability at 8 and 38 mM was 0.18+0.07 and 0.40+0.08, respectively (P=0.002). Bioavailability was higher in the MI group than in controls (P=0.01 at 8 mM and P50.001 at 38 mM). DHA-glucuronide was the sole biliary metabolite. 4 Hepatic microsomal studies of DHA-glucuronide formation showed a signi®cantly lower V max , but no signi®cant change in K m , in MI compared to control livers (n=6). Intrinsic metabolic clearance (V max /K m ) was higher in control than in MI livers (5.2+1.3 and 2.5+1.4 ml min 71 mg 71 , respectively; P=0.006). 5 These studies demonstrate that DHA has a high, concentration-dependent hepatic extraction ratio that is reduced by 20 ± 30% in the P. berghei rodent malaria model. The impaired hepatic clearance of DHA in MI is attributable to a reduction in intrinsic metabolic clearance.

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Section: Introductionmentioning

confidence: 99%

“…The pharmacokinetic parameters were consistent with data reported from similar clinical studies using selective high performance liquid chromatography (h.p.l.c.) assays (Batty et al, 1996(Batty et al, , 1998aBenakis et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

Assessment of the effect of malaria infection on hepatic clearance of dihydroartemisinin using rat liver perfusions and microsomes

Batty

Ilett

Edwards

et al. 1998

British J Pharmacology

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“…It is the most rapidly acting of the artemisinin derivatives, exhibiting rapid absorption after oral and intramuscular administration and rapid elimination [8]. Artesunate have been reported to be effective in uncomplicated, severe and multidrug resistant malaria.…”

Section: Introductionmentioning

confidence: 99%

Synergistic effect of aqueous extract of <i>Telfaria occidentalis</i> on the biological activities of artesunate in <i>Plasmodium berghei</i> infected mice

Adegbolagun¹,

Emikpe²,

Woranola³

et al. 2014

Afr H. Sci.

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Background: Resistance to most antimalarial drugs has encouraged the use of herbal preparations along with prescribed orthodox drugs. Objective: this study investigated effect of co-administration of aqueous extract of T. occidentalis leaves, commonly used as antimalarial and haematinic agent in Nigeria, and artesunate using P. berghei animal model. Methods: In vivo curative antiplasmodial effect of T. occidentalis (200mg/kg) alone and in combination with artesunate (2mg/kg) were evaluated using albino mice infected with 10 6 parasitized erythrocytes of P. berghei intraperitoneally. The haematological parameters: haemoglobin level, red blood cells and white blood cells and packed cell volume were monitored using standard methods. Results: Aqueous extract of T. occidentalis, artesunate and the combination gave 72.17±4.07%, 70.43± 4.27% and 85.43± 3.65% reduction in parasitaemia after 48hours respectively. A significant enhancement of the PCV was obtained with the co-administration of artesunate and aqueous extract (p < 0.01). Similar trends were also observed with heamatological parameters at 72 hours of administration. Conclusion: This study revealed a synergistic effect of the co-administration on parasite clearance rate of P. berghei infection in mice, with a significant enhancement of haematological parameters within 48 hours of administration. This indicates a rapid rate of recovery from plasmodial infections with the co-administration.

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“…13 Previously, the main methods for their quantification were electrochemical detection with detection limits of approximately 10 ng/mL by using sample volumes of approximately 0.5-1 mL plasma or post-column derivatization with methanolic alkali and subsequent ultraviolet detection with limits of detection of approximately 30 ng/mL. [14][15][16][17][18][19][20] Currently, the suitable method for quantification of these compounds in plasma is liquid chromatography coupled with mass spectrometry detection (LC-Ms or LC-MS/MS) with quantification limits of approximately 1 ng/mL using only 50-μL plasma sample volumes. [21][22][23][24][25] However, some of the problems encountered the latter bioanalytical methods include lack of appropriate stable isotope-labeled AS and DHA internal standards, in addition to expensive solid phase extraction cartridges that most commonly used for extraction of AS and DHA from biological samples.…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics of Artesunate Alone and in Combination with Sulfadoxine/Pyrimethamine in Healthy Sudanese Volunteers

Matar

Awad

Elamin

2014

The American Journal of Tropical Medicine and Hygiene

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Abstract. Artesunate (AS) in combination with sulfadoxine/pyrimethamine (SP) is the first-line therapy for management of uncomplicated Plasmodium falciparum malaria in Sudan. The objective of this study was to assess the potential impact of SP on the pharmacokinetics of AS and its active metabolite, dihydroartemisinin (DHA), in healthy adults. A single-dose, randomized, open-label, crossover study design with a washout period of three weeks was performed with 16 volunteers. After oral administration of AS alone or in combination with SP, T max values of AS and DHA were significantly prolonged in the combination group (P 0.05). However, there was no significant effect on the other pharmacokinetic parameters (P 0.05). The t 1/2 values of AS and DHA were significantly higher in females than in males (P 0.05). The present findings suggest that co-administration of SP with AS has no clinically relevant impact on the pharmacokinetics of AS or DHA in healthy persons.

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Pharmacokinetics of Artemisinin and Artesunate after Oral Administration in Healthy Volunteers

Cited by 98 publications

References 0 publications

Assessment of the effect of malaria infection on hepatic clearance of dihydroartemisinin using rat liver perfusions and microsomes

Assessment of the effect of malaria infection on hepatic clearance of dihydroartemisinin using rat liver perfusions and microsomes

Synergistic effect of aqueous extract of <i>Telfaria occidentalis</i> on the biological activities of artesunate in <i>Plasmodium berghei</i> infected mice

Pharmacokinetics of Artesunate Alone and in Combination with Sulfadoxine/Pyrimethamine in Healthy Sudanese Volunteers

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