Biomedical subjects

T Taylor

Publications and source records attributed to T Taylor.

At least 199 records · Page 11Linked to original sources

PubMed1976

Serum concentrations of methaqualone after repeated oral doses of a combination formulation to human subjects.

Concentrations of methaqualone have been measured in the serum of five male human subjects receiving five consecutive evening doses of a combination formulation containing methaqualone (250 mg), carbromal (300 mg) and benactyzine (0.33 mg) in each tablet. After administration of the first dose, mean peak serum concentrations of methaqualone (1.2 mug/ml) occurred at 3 h. After obtaining peak levels, mean concentrations of methaqualone declined rapidly during the next 6 h and thereafter more slowly during the next 18 h. After administration of the last (fifth) dose, mean peak serum concentrations of methaqualone (1.9 mug/ml; 1.5 mug/ml above the predose level) occurred at 2 h. After attaining peak levels, mean concentrations of methaqualone declined rapidly during the next 6 h, and thereafter more slowly, with a half-life of approximately 10 h. Mean concentrations of methaqualone in serum samples 24 h after the second, third, fourth or fifth doses were not significantly different (0.3 mug/ml - 0.6 mug/ml) during this period of dosing. This suggests that significant accumulation of methaqualone in the serum did not occur during a period of five consecutive evening doses of the combination formulation.

Administration, Oral↗

PubMed1976

Serum concentrations and bioavailability of rifampicin and isoniazid in combination.

The bioavailability of rifampicin and isoniazid from formulations containing these drugs in combination has been compared to that from formulations containing either drug alone. No formulation-related differences in either rates or extent of bioavailability were found after administration of each formulation. Mean peak serum concentrations of rifampicin (8.2-11.7 mug/ml) occurring 2 to 4 h after doses of 600 mg, and isoniazid (3.6-4.8 mug/ml) occurring 0.5 to 1 h after doses of 300 mg, were similar to those reported in the literature.

Adolescent↗

PubMed1976

The metabolic fate of the coronary vasodilator 4-(3,4,5-Trimethoxycinnamoyl)-1-(N-pyrrolidinocarbonylmethyl)piperazine (cinepazide) in the rat, dog and man.

1. An oral dose of the coronary vasodilator 4-(3,4,5-trimethoxy[14C]cinnamoyl)-1-(N-pyrrolidinocarbonylmethyl)piperazine was well absorbed and more than 60% of the dose was excreted within 24 h. In 5 days, rats, dogs, and man excreted in the urine and faeces respectively 36.7% and 58.3%, 33.4% and 68.6%, and 61.3% and 38.1% dose. Faecal radioactivity was probably excreted via the bile. 2. Plasma concentrations of radioactivity reached a maximum within about 1 h in all three species and declined fairly rapidly (t0.5 less than 3 h). For several hours, more than 50% of the plasma radioactivity was due to unchanged drug. After correction for dose and body weight (normalization), peak plasma concentrations of unchanged drug in man, rat and dog were in the approximate ratio 100 :30:1. 3. Similar metabolites were excreted by the three species, but the relative proportions differed. Rats and man excreted 17.2% and 15.9% respectively as unchanged drug in the urine whereas dogs excreted only 3.6%. Rat bile and urine contained 4.3% and 9.8% dose respectively as glucuronides of the mono-O-demethylated compounds and dog and human urine contained 9.0% and 2.6% respectively of these metabolites. The corresponding pyrrolidone accounted for 2.5%, 5.5% and 5.1% respectively in rat, dog and human urine. Complete O-demethylation also occurred since 4-(3,4,5-trihydroxycinnamoyl)-1-(N-pyrrolidinocarbonylmethyl)piperazine was present in rat faeces (22.1% dose).

Animals↗

PubMed1976

Absorption and disposition of econazole nitrate after application to the skins and vaginas of rabbits.

1. The absorption and tissue distribution of radioactivity has been studied in rabbits after application of a cream containing 10 mg of the 3H-labelled 1-(2,4-dichloro-beta-[(p-chlorobenzyl)oxy]phenethyl) imidazole nitrate (econazole nitrate, Pevaryl) to the normal or abraded skins of rabbits. 2. Approximately one-third of the dose was absorbed through the occluded normal skins of rabbits during 8 days, mainly during 7 to 24 h. In the same time interval, slightly more of the dose was absorbed through the occluded abraded skins of rabbits at slightly greater rates. Co-formulation of triamcinolone acetonide in the cream reduced and delayed the peak rates of absorption through normal and abraded skin, but the extent of absorption during 8 days was similar in the presence or absence of triamcinolone acetonide. 3. After application to normal skin or abraded skin, the peak of mean concentrations in the plasma of 220 ng/ml (range 132-276 ng/ml) or 307 ng/ml (range 270-321 ng/ml), respectively, occurred at 24 h. Tissue distribution of radioactivity was similar after application to normal or abraded skin, and concentrations were highest in the liver, kidneys and gastrointestinal tract (which are the organs of biotransformation and excretion) and also in the adrenals and to a lesser extent in the uterus, ovaries and untreated skin. 4. After application of a cream containing 5 mg of 3H-econazole nitrate to the vaginas of rabbits, approximately one-third of the dose was absorbed during 8-24 h, and rates of excretion were higher through the more permeable vaginal membrane. 5. After vaginal doses of 5 mg, a peak concentration of 209 ng/ml occurred at 6 h in the plasma. Tissue concentrations of radioactivity after vaginal doses were highest in liver, kidneys, gastrointestinal tract, adrenals and ovaries, and the tissue distribution was similar to that observed after cutaneous doses.

Administration, Oral↗

PubMed1976

Use of pharmacokinetics to predict the distribution of pantothenate in dogs.

On the basis of plasma concentrations of pantothen[14C]ate, after its intravenous administration, a three compartment open model was proposed to predict the pharmacokinetics of pantothenate in dogs. The model assumed a central compartment comprising the plasma and other extracellular fluids, and distribution into two other peripheral compartments, one of which included the liver. Elimination of unchanged pantothenate was assumed to occur by metabolism from the compartment which included the liver. Distribution of pantothen[14C]ate from the plasma compartment into the liver compartment was shown to be very rapid; during 10 min after intravenous administration about 80 per cent of the dose had been cleared from the plasma compartment. The model successfully predicted the influence (first pass effect) of the liver on the fraction of an oral dose which reached the peripheral plasma unchanged.

Administration, Oral↗

PubMed1976

Antilipidemic drugs. Part 4: The metabolic fate of the hypolipidemic agent isopropyl-[4'-(p-chlorobenzoyl)-2-phenoxy-2-methyl]-protionate (LF 178) in rats, dog and man.

The excretion and plasma concentrations of radioactivity and chromatographic patterns of radioactive components in plasma and excreta have been compared in rats, dogs and man after oral doses of the hypolipidemic agent isopropyl-[4'-(p-chlorobenzoyl)-2-phenoxy-2-methyl]-propionate (LF 178; procetofene; Lipanthyl¿). 2. In rats, 48.1% of a single dose of 25 mg/kg was excreted in the urine, and 48.6% in the faeces. In dogs, 23.1% of a single dose at the same level was excreted in the urine, and 71.8% in the faeces, but 88.1% of a dose of 300 mg to man was excreted in the urine, and only 5.1% in the faeces. Peak levels of radioactivity in the plasma of all three species studied were similar (20--30 mug/ml) after doses at these levels and concentrations declined thereafter with half-lives of 7--24 h in rats and dogs, and 7 h in man. The half-life of radioactivity concentrations in rat plasma was not altered by repeated daily doses for 7 days. 3. Whole-body autoradiography of rats showed that radioactivity was largely associated with the liver, kidneys and gut, which are the organs of biotransformation and excretion, although relatively high levels were present in lungs and blood, and small amounts of radioactivity had a widespread distribution into some peripheral tissues during 2--7 h after dosing. 4. The available chromatographic evidence indicated that the most important biotransformation pathway appeared to be ester hydrolysis to LF 178 acid and formation of water soluble conjugates of this acid. This pathway appeared similar to that of the related drug clofibrate (ethyl p-chlorophenoxyisobutyrate).

Administration, Oral↗

PubMed1975

Topical analgesia before tracheal intubation.

The major toxic effects of local analgesic drugs are regarded as due to over-dosage. A technique of topical analgesia for tracheal intubation using lignocaine is described based on spraying the pyriform fossae to effect a superior laryngeal nerve block combined with topical analgesia of larynx and trachea which avoids excessive exposure of the lowere airway to the local analgesic. The results show lower levels of venous blood lignocaine with slower absorption of the agent than when similar doses are applied to the trachea. This method is accordingly recommended.

Administration, Topical↗

PubMed1975