Pharmacokinetic study of the novel, synthetic trioxane antimalarial compound 97-78 in rats using an LC-MS/MS method for quantification.

The present study has been designed to investigate the pharmacokinetic parameters of the novel trioxane antimalarial 97-78 (US Patent 6316493 B1, 2001) in male and female rats after single oral and intravenous administration. The pharmacokinetic profile of 97-78 was investigated in the form of its completely converted metabolite 97-63 after dose administration. Quantification of metabolite 97-63 in rat plasma was achieved using a simple and rapid LC-MS/MS method.

Preclinical pharmacokinetics, dose proportionality, gender difference and protein binding study of 16-dehydropregnenolone, an antihyperlipidemic agent, in rats.

Objectives: This manuscript addresses key pharmacokinetic issues in support of the development of a potent candidate lipid-lowering drug molecule, 16-dehydropregnenolone (DHP).

Methods: Liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) assay for simultaneous estimation of DHP and its metabolites, including 5-pregnene-3β-ol-16, 17-epoxi-20-one (M(1) ) was validated in male and female Sprague-Dawley rat plasma and applied to different studies. Pharmacokinetic studies of DHP after intravenous and oral administration were carried out to assess any gender effect.

Interspecies comparison of the pharmacokinetics and oral bioavailability of 99-357, a potent synthetic trioxane antimalarial compound.

The pharmacokinetic data obtained in lower animals is of considerable importance in drug discovery and development. The objective of the present study was to generate in vitro and in vivo preclinical pharmacokinetic data of 99-357, a synthetic trioxane antimalarial, in rats and rabbits and to scale-up the data in order to apply for further studies. The pharmacokinetic profile of 99-357 was investigated after both intravenous and oral dose in rats and rabbits.

Pharmacokinetics of the proton pump inhibitor CDRI-85/92 and its ester prodrug, a new H+/K(+)-ATPase inhibitor with anti-ulcer activities, after oral doses in rats.

5-Styryl-4,5-cis-1,3-oxazole-2-one-4-carboxylic acid (CDRI-85/92) is a new proton pump inhibitor presently in advanced stage of preclinical trials as antiulcer pharmacophore. Since proton pump inhibitors are prodrugs requiring activation in acid environment, an ester prodrug of CDRI-85/92 was also synthesized. In view of the importance, a pharmacokinetic study of CDRI-85/92 and its ester prodrug was conducted after oral doses in rats.

Pharmacokinetics and excretion of the novel anti-tuberculosis compound 1,2:5,6-di-O-isopropylidene-3-O-(phenyl cyclopropyl methanonyl)-alpha-D-glucofuranose (S-001-14) after oral doses in rats. Development of a sensitive and reproducible high performance liquid chromatography-UV method for the determination of the test compound in rat serum.

A sensitive and reproducible high performance liquid chromatography (HPLC)-UV method for the determination of the novel anti-tuberculosis compound 1,2:5,6-di-O-isopropylidene-3-O-(phenyl cyclopropyl methanonyl)-alpha-D-glucofuranose (S-001-14) has been developed and validated in rat serum, urine and feces. Following extraction with hexane at alkaline pH, samples were separated on a reverse phase C18 column and quantified using UV detection at 267 nm. The mobile phase was 70% acetonitrile in ammonium acetate buffer (10 mmol/L, pH 6.

Absorption, protein binding, pharmacokinetics and excretion of the anti-ischemic and anti-hypertensive arylpiperazine derivative CDRI-93/478 in rats.

CDRI-93/478 (1- [4-(4-fluorophenyl) piperazine-1-yl]-3-(2-oxopyrrolidin-1-yl) propane hydrochloride, an arylpiperazine derivative, is a potent anti-ischemic and anti-hypertensive agent and is in advanced stage of preclinical trials. In order to develop CDRI-93/478 into a clinical agent, the absorption, protein binding, pharmacokinetics, and excretion of the compound were investigated in male Sprague-Dawley rats. Oral absorption was evaluated in situ and in vivo, using the portal-venous concentration difference method.

A sensitive and selective liquid chromatographic tandem mass spectrometric assay for simultaneous quantification of novel trioxane antimalarials in different biomatrices using sample-pooling approach for high throughput pharmacokinetic studies.

In the present studies, to give momentum to traditionally low throughput pharmacokinetic screening, a bioanalytical method based on the concept of sample pooling for simultaneous bioanalysis of multiple compounds is discussed. A sensitive, selective, specific and rapid HPLC/ESI-MS/MS assay method was developed and validated for the simultaneous quantitation of three novel trioxane antimalarials (99-357, 99-408 and 99-411) in rat plasma using trioxane analogue as internal standard. The suitably validated bioanalytical method was then further extrapolated to rabbit and monkey plasma by performing partial validation.

In Vitro and In Vivo pharmacokinetic studies of bulaquine (analogue of primaquine), a novel antirelapse antimalarial, in rat, rabbit and monkey--highlighting species similarities and differences.

Bulaquine (BQ) is a potent antirelapse antimalarial developed by CDRI, India. Bulaquine was rapidly absorbed in rats and rabbits with no distinct absorption phase while in monkeys a variable irregular absorption profile was observed. BQ was extensively converted to primaquine (PQ) after oral administration and the conversion was maximum in rats and minimum in rabbits, which is possibly due to the species difference.

Effect of concurrently coadministered drugs on the pharmacokinetic/pharmacodynamic profile of centchroman, a nonsteroidal oral contraceptive, in rats.

Introduction: Centchroman (international nonproprietary name: ormeloxifene) is a nonsteroidal selective estrogen receptor modulator, oral contraceptive, anticancer and antiosteoporotic agent that is intended for long-term use by women. In view of the vast clinical applications and interactions of steroidal oral contraceptives with commonly used therapeutic agents, the interaction potential of certain concomitantly administered therapeutic agents was investigated in terms of postcoital contraceptive efficacy (pharmacological) and the pharmacokinetic profile of centchroman in female Sprague-Dawley rats. The coadministered drugs used in the study were ciprofloxacin, cefixime, amoxicillin, metronidazole, amlodipine, atenolol, theophylline, metformin, pioglitazone and glibenclamide.

Analysis and pharmacokinetics of bulaquine and its major metabolite primaquine in rabbits using an LC-UV method--a pilot study.

A precise and reproducible HPLC assay has been developed and validated for simultaneous determination of bulaquine (BQ) and its metabolite primaquine (PQ) in rabbit plasma. The method, applicable to 0.5 ml plasma, involves double extraction of samples with n-hexane: isopropanol (98:2, v/v) containing dimethyl octylamine (DMOA) (0.

LC determination of a sulphur mustard decontaminant CC-2 in rat serum.

A high-performance liquid chromatographic (HPLC) method was developed for the analysis of N,N'-Dichlorobis (2,4,6-trichlorophenyl) urea (CC-2), a potent sulphur mustard decontaminant, in rat serum. The HPLC analysis, applicable to 0.5 ml volumes of serum, involved double extraction of serum samples with diethyl ether at alkaline pH followed by separation on a RP-18 column and the use of UV detector at 230 nm.

A sensitive LC assay for the simultaneous determination of centbutindole and its metabolite in rat serum using fluorescence detection.

Centbutindole (+/-) 2-gamma-[(p-fluorobenzoyl)propyl]-1, 2, 3, 4, 6, 7, 12, 12a-octahydro-pyrazino (2', 1': 6, 1) pyrido [3, 4-b] indole (I), is a new neuroleptic agent developed by Central Drug Research Institute, India. In the present study, a high performance liquid chromatography (HPLC) assay method for the simultaneous assay for I and its metabolite (II) in rat serum was developed and validated. The present method requires only 1 ml of serum with detection levels similar to that reported earlier using 4 ml serum.