The pharmacokinetics of artemisinin after administration of two different suppositories to healthy Vietnamese subjects.

Abstract

Abstract. Eight healthy Vietnamese male subjects received 400 mg artemisinin formulated into fatty suppositories (FS), and six different subjects received 500 mg of artemisinin formulated in polyethylene glycol suppositories (PEGS). Plasma concentrations were measured by high-performance liquid chromatography with electrochemical detection; concentration versus time curves were analyzed with nonparametric methods. No statistically significant differences were found between the two formulations. The maximum concentration (Cmax) was 100 Ϯ 102 g/L (mean Ϯ SD, range ϭ 24-330) g/L (FS), the pharmacokinetic lag time (Tlag) was 1.3 Ϯ 1.0 hr (range ϭ 0-3) (FS), and the time of the maximum concentration (Tmax) was 7.1 Ϯ 2.1 hr (range ϭ 3-10) hr (FS). Because artemisinin is not available for intravenous dosage, absolute bioavailability cannot be assessed. However, compared with a previous study on oral artemisinin in healthy Vietnamese subjects, bioavailability relative to oral administration was estimated to be approximately 30%. We conclude that therapeutic blood concentrations of artemisinin can be reached after rectal dosage. The dose after rectal administration should probably be higher than after oral administration; doubling or tripling the oral dose might be necessary, which would imply a rectal dose of at least 20 mg/kg of body weight given twice a day.Artemisinin is a drug from a new and promising class of antimalarials.1-3 This class includes the parent compound artemisinin, and its first-generation derivatives artemether, arteether, artesunate, and dihydroartemisinin. Clinical use in Asia for 20 years has shown that artemisinin compounds are very effective, with rapid parasite clearance, against multidrug-resistant Plasmodium falciparum. 2 It seems to be a very safe drug; to date no serious adverse effects have been reported in humans. One of the differences among these compounds is water solubility, and therefore the possibility of parenteral administration. At the present time, there is no pharmaceutical preparation of artemisinin for parenteral administration. In the treatment of severe and complicated malaria, parenteral administration of drugs is usually necessary, and rectal administration could be a feasible alternative, especially in remote areas. Although in one preliminary pharmacokinetic study very low, and probably subtherapeutic plasma concentrations were reported after rectal dosage 4 , clinical trials with artemisinin or artesunate suppositories in severe malaria have shown good results. 5-8 We therefore determined the pharmacokinetics of artemisinin suppositories that are presently available in Vietnam; these suppositories have been used in recent therapeutic trials. 5,6 The latter suppositories are fat based; we compared them with hydrophilic (i.e., polyethylene glycol)-based suppositories. METHODSSubjects and experimental design. Fourteen healthy male Vietnamese subjects were recruited at the Institute of Clinical Research in Tropical Medicine of the Bach Mai Hospital, Hanoi. The mean Ϯ SD ch...

Chloroquine reduces urinary excretion of cloxacillin when it is administered concurrently with ampicillin-cloxacillin combination

“…The eight volunteers included 6 males and 2 females aged between 21 and 30 years (mean, 25.3 ± 3.2 years), and weighing between 51 and 69 kg (mean, 61 ± 5.7 kg). The continuation of the study with the eight volunteers is supported by recent kinetic studies that have reported limited number of subjects 6,7,8 . Consent was obtained from each volunteer after full explanation of the protocol.…”

Pharmacokinetic and Pharmacodynamic Profiles of Rapid-Acting Artemisinins in the Antimalarial Therapy

“…The absorption of QHS capsules with 1.21 hr half-life was slower than the absorptions of AS and DHA drugs, suggesting that the slow reduction of parasitemia may have resulted from the slow absorption and low antimalarial potency. Compared with oral AS and DHA study, oral QHS appeared to have very low bioavailability of 30% [74,75] and low antimalarial potency with cultured P. falciparum [76].…”

Determination of artemisinin in human serum by high-performance liquid chromatography with on-line UV irradiation and peroxyoxalate chemiluminescence detection

“…According to Ashton et al (1998), plasma concentration after single oral clinical dose of 500 mg of artemisinin is 450 ng/mL at a maximum time of 2.3 h. Koopmans et al (1999) also stated 100 ng/mL as the lower maximum concentration after rectal administration at a maximum time of 7.1 h. The sensitivity (17.5 ng/mL) of artemisinin in spiked human serum by the proposed HPLC-PO-CL method is lower than cited plasma concentrations (100 and 450 ng/mL) after a single clinical dose, therefore the proposed HPLC-PO-CL method should be useful for pharmacokinetic and clinical studies of artemisinin in malarial patients.…”