Search PubMed⌕ Search

Biomedical subjects

A S Fowle

Publications and source records attributed to A S Fowle.

At least 19 recordsLinked to original sources
PubMed1986

Comparative disposition of codeine and pholcodine in man after single oral doses.

Four healthy male subjects received single oral doses of 15, 30 and 60 mg of codeine and pholcodine according to a balanced cross-over design with an interval of 7 days between the six treatments. Blood samples were collected for 8 h after each drug administration. In phase 2 of the study six different male volunteers received single oral doses of 60 mg of codeine and pholcodine with a 14 day interval between successive drug treatments. Blood was sampled for 12 h after codeine and 121 h after pholcodine administration. Plasma concentrations of free (unconjugated) and total (unconjugated plus conjugated) codeine, pholcodine and morphine were determined by radioimmunoassay and selected pharmacokinetic parameters were derived from these data. Pharmacokinetics of both drugs were independent of dose. Codeine was absorbed and eliminated relatively rapidly [elimination t1/2 = 2.3 +/- 0.4 h (mean +/- s.d.)]. While codeine kinetics were adequately described by a one-compartment open model with first-order absorption, a two-compartment model was required to describe pholcodine elimination from plasma (t1/2,z = 37.0 +/- 4.2 h). Plasma concentrations of conjugated codeine were much greater than those of the unconjugated alkaloid. By contrast, pholcodine appeared to undergo little conjugation. Biotransformation of codeine to morphine was evident in all subjects, although the extent of this metabolic conversion varied considerably between subjects. Morphine was not detectable in the plasma of any subject after pholcodine administration.

Administration, Oral↗
PubMed1986

Human gastrointestinal absorption of acyclovir from tablet duodenal infusion and sipped solution.

On two occasions at least 1 week apart, nine healthy male volunteers were administered in random order either 2 X 200 mg (1.8 mmol) acyclovir tablets or 400 mg of acyclovir in 500 ml of 5% dextrose solution which was infused at constant rate into the duodenum over 4 h. Six of the subjects subsequently sipped the same solution at the rate of 10.4 ml in each 5 min period for 4 h. Blood and urine were sampled over 24 h for each mode of administration. Acyclovir was assayed by radioimmunoassay. Mean areas under the plasma concentration-time curves (AUCs) +/- s.d. for tablet (T), intraduodenal infusion (I) and sipping (S) were, respectively: T = 14.7 +/- 5.1; I = 24.6 +/- 5.1; S = 28.4 +/- 9.5 (n = 6) mumol l-1 h. AUCs for I and S were significantly greater than that for T (2P less than 0.05). Mean apparent maximum plasma concentrations (Cmax) +/- s.d. were T = 3.8 +/- 1.5; I = 4.8 +/- 0.9; S = 5.1 +/- 1.5 mumol l-1. This trend to higher values for I and S was not significant. Mean apparent plasma disappearance half-lives (t1/2) +/- s.d. were respectively T = 2.3 +/- 0.4; I = 2.7 +/- 0.5; S = 3.0 +/- 0.2 h, I being significantly greater than T (2P less than 0.05), as was S greater than T (2P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Acyclovir↗
PubMed1985

Pharmacokinetics and Pharmacodynamics of procyclidine in man.

The pharmacokinetics and pharmacodynamics of procyclidine (10 mg) after oral and intravenous administration were studied in six healthy volunteers. Treatment order was randomised and the study was placebo-controlled and conducted blind. After oral dosing the mean peak plasma concentration was 116 ng/ml and mean bioavailability was 75%. After both oral and intravenous dosing the mean values for the volume of distribution, total body clearance and plasma elimination half-life of procyclidine were in the order of 1 l/kg, 68 ml/min and 12 h respectively. Autonomic effects were maximal within 0.5 h of intravenous administration and at about 1-2 h after oral dosing. Significant effects on pupil diameter, visual near point, salivary secretion and heart rate occurred after intravenous treatment and similar but less marked effects occurred after the oral dose. Significant autonomic effects were still detectable 12 h after both forms of treatment.

Administration, Oral↗
PubMed1984

Tolerance and pharmacokinetics of A515U, an acyclovir analogue, in healthy volunteers.

A515U (6-deoxyacyclovir) is an analogue of acyclovir devoid of antiviral activity in vitro but which is well absorbed and undergoes conversion to acyclovir after oral administration to rats. The tolerance and pharmacokinetics of various doses of A515U have been studied in 8 healthy volunteers. Single oral doses of 25, 50, 100, 200 and 400 mg A515U and 400 mg acyclovir for comparison were administered to the volunteers at weekly intervals. Concentrations of the parent drug and acyclovir were determined in plasma and urine. The prodrug was well tolerated and did not cause adverse reactions or changes in haematological or biochemical variables. It was well absorbed and conversion to acyclovir was rapid and extensive at all doses. Plasma concentrations of acyclovir achieved with 50 mg A515U orally were comparable to and less variable than those produced by 400 mg acyclovir. A515U was rapidly cleared with a short plasma elimination half life of approximately 0.5 h. The attainment of high plasma concentrations of acyclovir by oral administration of a prodrug may represent an important advance in antiviral chemotherapy.

Absorption↗
PubMed1983

Failure of bupropion to affect prolactin or growth hormone in man.

In a double-blind crossover design, 5 male and 5 female volunteers received 5 different oral single-dose bupropion treatments (12.5 mg to 100 mg). Analyses of plasma prolactin and growth hormone levels revealed no significant drug related effects compared to placebo.

Adult↗
PubMed1982

Plasma levels of a novel antidysrhythmic agent, meobentine sulfate, in humans as determined by radioimmunoassay.

A radioimmunoassay for the quantitation of meobentine sulfate, a novel antidysrhythmic and antifibrillatory agent in biological fluids, is described. Antisera were raised in rabbits in response to immunization with a conjugate of bovine serum albumin and a meobentine analog with a propionic acid sidechain ortho to the methoxyl group. These antisera have low affinities for N- and O-desmethylmeobentine metabolites, which show less than 5% cross-reaction in radioimmunoassay procedures employing either tritiated or radioiodinated radioligands. The radioimmunoassay using[125I]meobentine was capable of detecting less than 0.4 ng/ml (40-pg mass) of meobentine. This assay was used to demonstrate the absorption of meobentine in humans after oral administration and also permitted studies of meobentine sulfate disposition in human plasma following two (2.5 and 5 mg/kg) oral doses. Mean peak meobentine concentrations in plasma occurred 3 hr postdose in both cases and were 230 and 451 ng/ml following the 2.5- and 5-mg/kg doses, respectively. The approximate mean terminal half-life after all treatments was 12 hr.

Animals↗
PubMed1981

The effects of some organic solvents on the absorption of digoxin by man.

Ten healthy subjects took each of 6 different solutions of 0.5 mg digoxin in a study of the effect of different solvents on absorption. Bioavailability was measured by the urinary recovery of digoxin in the eight days after each dosing. The six liquid preparation were aqueous solution, an organic solvent complex (lanoxicaps fill) for which solvent assisted absorption has been suggested, digoxin elixir, and three different solutions each comprising a single organic solvent in the concentration used in lanoxicaps plus water to make up the balance. Pure aqueous solution and lanoxicaps fill had the highest bioavailability as judged by urinary recovery but there was no significant different at the 5% level between the urinary recovery from the lanoxicap fill, the elixir and the two preparations with water as the preponderant solvent. It is concluded that the greater bioavailability of digoxin from lanoxicaps than from tablet formulations is more likely to ve due at least in part to delivery of digoxin already dissolved than to the identities of the solvents. The rate of intestinal digoxin uptake may possibly influence the degree of urinary recovery.

Adult↗
PubMed1980

Effects of pseudoephedrine and triprolidine, alone and in combination, on symptoms of the common cold.

A total of 466 healthy adults from four different regions of England entered a double-blind, randomised trial to test the effectiveness of an antihistamine (triprolidine) and a decongestant (pseudoephedrine), alone or in combination, in relieving symptoms of the common cold. During the study 199 subjects reported a total of 243 colds. Subjects recorded the severity of 12 symptoms during treatment and noted separately the severity of a further seven symptoms that represented unwanted effects of treatment or served as an index of suggestibility. They were then asked about their overall improvement in symptoms during treatment and whether they thought they had taken placebo. Sneezing, nasal obstruction, and overall response to treatment were significantly improved (p <0.01) with psuedoephedrine or pseudoephedrine and triprolidine compared with placebo.

Clinical Trials as Topic↗
PubMed1980

Effects of intravenous infusion of prostacyclin (PGI2) in man.

Prostacyclin infused intravenously in human volunteers induces ex vivo inhibition of platelet aggregation, tachycardia and hypotension. The inhibition of platelet aggregation is obtained with slightly lower doses than those which exhibit cardiovascular effects. The cardiovascular effects disappeared within a few minutes after discontinuing the infusion of prostacyclin but the platelet effects were longer lasting. Prostacyclin did not have any effect on platelet count, platelet factor 3, accelerated partial thromboplastin time, prothrombin time, euglobulin clot lysis time, fibrinogen degradation products, blood glucose concentration or urine sodium potassium ratio.

Adult↗
PubMed1975

A comparison of triprolidine and clemastine on histamine antagonism and performance tests in man: implications for the mechanism of drug induced drowsiness.

The effects of triprolidine hydrochloride 1.25, 2.5 and 5 mg, clemastine 1 and 2 mg and lactose dummy administered orally, in a balanced order, at weekly intervals to 12 healthy volunteers, on the flare and weal responses to intradermal histamine injection, and also on both subjective effects and objective psychomotor tests were examined. The histamine response was significantly larger at 09.00 h falling through the day but increasing by late afternoon. Triprolidine produced a dose-related antagonism of both flare and weal response maximal at 3 h and wearing off after the lower doses at 8 h. Clemastine by contrast produced poor antagonism of histamine at 3 h but a marked effect at 5.5 and 8 h. Auditory vigilance was significantly (p less than 0.05) impaired by all doses of triprolidine 1 to 2 h after administration, but no change followed clemastine at this time. When tested 6 to 7 h after administration significant impairment followed both doses of clemastine but only the 5 mg dose of triprolidine. Both drugs prolonged reaction time in a dose-related manner at 2.5 and 5.0 h but the effects had worn off at 7 h. Digit symbol substitution was impaired by the top doses of both antihistamines but short term memory was unaffected. Subjective effects measured using analogue lines reflected the effects in the vigilance test, in that drowsiness and mental impairment were noted early after triprolidine, while clemastine produced maximal effects at 5 h. Subjects were ranked in order of magnitude of inhibition of both flare and weal, and impairment of vigilance, prolongation of reaction time and subjective drowsiness score. There was no indication of a significant correlation, using Spearman's test, between antagonism of histamine and effects on the central nervous system.

Adult↗