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D R Hawkins

Publications and source records attributed to D R Hawkins.

103 records · Page 6Linked to original sources
PubMedDate not supplied

The metabolic fate of 11-bromo[15-3H]vincamine in man.

During 5 days following a single oral dose of 3H-11-bromovincamine (40 mg) to two human subjects, means of 55% and 27% of the 3H dose were excreted in the urine and faeces respectively, mainly within 24 and 48 h. Mean plasma concentrations of 3H reached a peak (1900 ng equiv./ml) at 1 h after dosing and declined biphasically with half-lives of 5 h and 11 h which were similar to half-lives for urinary excretion of 3H. Parent drug and 11-bromovincaminic acid were the major dose-related components in plasma at 1.5 and 3 h. Mean plasma concentrations of 11-bromovincamine reached a peak (620 ng/ml) at 0.75 h and declined biphasically with half-lives of about 1 h and 5 h. The major urinary metabolite was 11-bromovincaminic acid (31% dose). Also present in urine were 11-bromovincamine (3%), 11-bromoapovincamine (1%) and 2 unknown metabolites (9% and 6%). Similar metabolites were detected in faecal extracts. If inadequately stored in biological samples, 11-bromovincamine could be hydrolysed to 11-bromovincaminic acid and be epimerised to 11-bromo-epivincamine.

Adult↗
PubMedDate not supplied

Metabolism of the anti-depressant lortalamine.

Humans excreted an oral dose of 5 mg of the anti-depressant lortalamine (radiolabelled with carbon-14) mainly in the urine (98% during 5 days). Plasma 14C concentrations were highest (about 44 ng equiv./ml) between 1.5-3 h when the corresponding concentrations of unchanged drug were about 17 ng/ml. Unchanged drug concentrations appeared to decline with a half-life of about 5 h. Concentrations of 14C then declined rapidly and were below the limits of detection (12 ng equiv./ml) at 24-36 h. Measurement of whole-blood 14C concentrations showed that there was some uptake into the blood cells (about 65% of the peak plasma 14C level). Radioactivity in the urine was mainly associated with unchanged drug and three metabolites. The major metabolite (about 50% urinary 14C) was identified by mass spectrometry as the N-demethylated compound and another metabolite as a keto derivative of lortalamine where oxidation had occurred in the piperidine ring.

Adult↗
PubMedDate not supplied

New taxanes from Taxus brevifolia.

The isolation of two taxanes from Taxus brevifolia Nutt. is described, together with the isolation of two acetylated taxol derivatives from an acetylated fraction from the same plant. The compounds were identified on the basis of their spectroscopic properties as taxa-4(20),11-diene-2 alpha, 5 alpha, 7 beta, 9 alpha, 10 beta, 13 alpha-hexaol 2,7,9,10,13-pentaacetate (1) (decinnamoyltaxinine J), 10-deacetylbaccatin III (2), taxol 2',7-diacetate (3), and 10-deacetyltaxol 2',7-diacetate (4).

Antineoplastic Agents, Phytogenic↗
PubMedDate not supplied

Biotransformation of methyl 5-cyclopropylcarbonyl-2-benzimidazolecarbamate (ciclobendazole) in rats and dogs.

A major metabolite of ciclobendazole (methyl 5-cyclopropylcarbonyl-2-benzimidazolecarbamate) excreted in the urine, bile, and feces of rats was methyl 5-cyclopropylcarbonyl-6-hydroxy-benzimidazolecarbamate, established by comparison of the proton magnetic resonance and mass spectra with that of the authentic compound. This compound represented 8.2% and 7.1% of the dose, respectively, in extracts of 24-hr urine and 48-hr feces samples of rats, but was only a minor metabolite in dog urine (1% of the dose). The unchanged drug was only detected in dog feces, the major route of excretion of radioactivity in the dog. 5-Cyclopropylcarbonyl-2-amino-benzimidazole was present in rat urine (2.5% of the dose). A major metabolite in dog bile was probably 5-cyclopropylcarbinol-2-aminobenzimidazole, formed by loss of the methoxycarbonyl group and reduction of the carbonyl function in the 5-position.

Animals↗
PubMedDate not supplied

Determination of amitriptyline and its major basic metabolites in human urine by high-performance liquid chromatography.

A high-performance liquid chromatographic method for the routine, simultaneous determination of amitriptyline and its basic metabolites in human urine has been developed. 10-Hydroxylated metabolites are analyzed as their 10,11-dehydro analogs, and primary and secondary amines as their N-trifluoroacetyl derivatives. The use of gradient elution enables amitryptyline, nortriptyline trifluoroacetate, desmethylnortriptyline trifluoroacetate, and the corresponding 10, 11-dehydro analogs to be separated from both each other and from the internal standard used. In this way all six compounds may be conveniently measured in a single chromatogram, with good sensitivity and accuracy. Following administration of a single oral dose (25 mg) of amitriptyline hydrochloride to two human subjects, no unchanged drug was found in any of the urine samples analyzed up to 72 hr after dosing, and only small amounts of nortriptyline and desmethylnortriptyline were observed. 10-hydroxynortriptyline was the major biotransformation product (about 40% of the dose) in urine, with 10-hydroxyamitriptyline and 10-hydroxydesmethylnortriptyline present as minor metabolites. During 72 hr after administration, approximately 60% of the dose was recovered as these five metabolites.

Adult↗