The pharmacokinetics and bioavailability of dihydroartemisinin, arteether, artemether, artesunic acid and artelinic acid in rats.

The pharmacokinetics and bioavailability of dihydroartemisinin (DQHS), artemether (AM), arteether (AE), artesunic acid (AS) and artelinic acid (AL) have been investigated in rats after single intravenous, intramuscular and intragastric doses of 10 mg kg(-1). Plasma was separated from blood samples collected at different times after dosing and analysed for parent drug. Plasma samples from rats dosed with AM, AE, AS and AL were also analysed for DQHS which is known to be an active metabolite of these compounds.

Fatal neurotoxicity of arteether and artemether.

Artemisinin (qinghaosu) and several derivatives have been developed and are in use as antimalarial drugs but scant information is available regarding animal or human toxicity. Following a eight-day, multiple-dose, pharmacokinetic study of arteether (AE) (10 mg/kg/day [n = 6] and 20 mg/kg/day [n = 6]) in dogs, all high-dose animals displayed a progressive syndrome of clinical neurologic defects with progressive cardiorespiratory collapse and death in five of six animals. Neurologic findings included gait disturbances, loss of spinal and pain response reflexes, and prominent loss of brain stem and eye reflexes.

Neurotoxicity in animals due to arteether and artemether.

Several artemisinin (qinghaosu) derivatives have been developed and are in use as antimalarial drugs but scant animal or human toxicity data are available. We noted a progressive syndrome of clinical neurological defects with cardio-respiratory collapse and death in 5/6 dogs dosed daily for 8 d with intramuscular arteether (AE) at 20 mg/kg/d in a pharmacokinetic study. Neurological findings included gait disturbances, loss of spinal reflexes, pain response reflexes and prominent loss of brain-stem and eye reflexes.

Comparison of beta-artemether and beta-arteether against malaria parasites in vitro and in vivo.

The antimalarial activity of beta-artemether and beta-arteether was compared in three test systems: in vitro against chloroquine-resistant and chloroquine-sensitive Plasmodium falciparum parasites, in mice infected with P. berghei, and in Aotus monkeys infected with chloroquine-resistant P. falciparum.

Primaquine disposition in the isolated perfused rat liver: effect of mefloquine induced bile flow reduction.

The disposition of primaquine (0.75 mg, 5 microCi) has been investigated in the isolated perfused rat liver (IPRL) preparation alone and concurrently with mefloquine. In both groups, primaquine concentrations declined exponentially.

Pralidoxime chloride stability-indicating assay and analysis of solution samples stored at room temperature for ten years.

A high-performance liquid chromatographic (HPLC) method is described for quantitation of pralidoxime chloride and its decomposition products 2-carboxy-, 2-formyl-, and 2-(aminocarbonyl)-1-methylpyridinium chloride. These decomposition products and 2-cyano- and 2-(hydroxymethyl)-1-methylpyridinium chloride and 1-methyl-2(1H)-pyridinone were separated from pralidoxime chloride on a silica gel column using a mobile phase of acetonitrile:water (86:14) in which the aqueous component was 8.36 mM in tetraethylammonium chloride and 52.

Disposition of the antimalarial, mefloquine, in the isolated perfused rat liver.

The disposition of mefloquine has been investigated in the isolated perfused rat liver (IPRL) preparation after the administration of [14C]mefloquine HCl (3.8 mg, 4 microCi, quinoline ring labeled). Mefloquine underwent avid hepatic uptake within 10 min of dosing.

Analysis of the antimalarial, mefloquine, in blood and plasma using high-performance liquid chromatography.

An analytical method is described for the quantitation of mefloquine, a new antimalarial agent, in plasma and blood. A structurally similar quinolinemethanol compound, WR 184,806, is used as the internal standard. The method employs a three-step extraction procedure followed by reversed-phase high-performance liquid chromatography, and octanesulfonate is used as an ion-pairing reagent.

Subacute toxicity of primaquine in dogs, monkeys, and rats.

Certain derivatives of the 8-aminoquinolines have been shown to affect some blood constituents and haemopoiesis, to induce functional changes in the central nervous system, and to cause other organ lesions. The 8-aminoquinolines vary widely in their toxicity and ability to induce tissue damage in different laboratory animals. In the present study, the subacute toxicity of primaquine was studied in beagle dogs, rhesus monkeys, and albino rats.

The cardiovascular actions of WR-149,024 (1,18-diamino-7,13-diaza-9,10-dithiaoctadecane tetrahydrochloride).

1. The general cardiovascular properties of WR-149,024 (a straight chain sulphur-containing aliphatic amine) in dogs and cats are reported.2.