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Biomedical subjects

P J Morrison

Publications and source records attributed to P J Morrison.

At least 109 records · Page 6Linked to original sources
PubMed1986

The effects of domperidone on the absorption of levodopa in normal subjects.

The effect of simultaneous oral administration of 20, 40, or 80 mg domperidone on the pharmacokinetics of an oral 500 mg dose of levodopa was studied in eight normal women. No significant differences in maximum plasma levodopa concentration, the time of its attainment, or the area under the plasma levodopa concentration versus time profile occurred. Domperidone significantly reduced the incidence of adverse gastrointestinal effects due to levodopa administration.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1986

Comparison of pharmacokinetic profiles of single and multiple doses of a slow release Oros oxprenolol delivery system in young normotensive and elderly hypertensive subjects.

Oxprenolol in an Oros 8/130 sustained release osmotic pump system (equivalent to 120 mg oxprenolol hydrochloride in a conventional formulation and releasing 8 mg h-1) was given to eight normal young subjects (mean age 23 years) and eight elderly hypertensive patients (mean age 77 years). The plasma concentration-time profiles of oxprenolol were determined over 32 h using gas liquid chromatography after the initial dose and following seven doses. The elderly patients had a significantly higher AUC and maximum plasma oxprenolol concentration following both the first and final doses studied. It is unlikely that this difference is due to a prolonged absorption phase in the elderly patients. Reduced drug clearance seems the most probable explanation.

Adult↗
PubMed1985

Pharmacokinetic investigation of the absorption of oxprenolol from Oros delivery systems in healthy volunteers: comparison of in vivo and in vitro drug release.

The absorption kinetics of oxprenolol have been investigated in eight healthy volunteers after single dosing with 16/260 Oros drug delivery systems. Oxprenolol disposition kinetics in individual subjects were estimated from intravenous dose data. Loo-Riegelman analysis of the plasma concentration data indicated an extended duration of drug absorption for the Oros system. Initially, the in vivo absorption rate was similar to the in vitro release rate but after 5-6 h it slowed perceptibly. However, at later times similar in vivo and in vitro rates were again observed. The absolute bioavailabilities for prototype and clinical trial systems were shown to be similar, at approximately 42%, and no significant differences in plasma profiles or pharmacokinetic constants were detected between the two Oros forms. A comparison of plasma concentration data in seven subjects who received the prototype system on two occasions in separate studies indicated a consistent level of drug absorption from this preparation. Approximately 10-15% of the administered dose was found in Oros systems recovered from faeces. The quantity of drug remaining was poorly correlated with the observed areas under the plasma concentration-time curve.

Adult↗
PubMed1985

Effects of single and multiple doses of ketoconazole on adrenal function in normal subjects.

The plasma cortisol response to 0.25 mg tetracosactrin given by intramuscular injection was suppressed by nine oral doses of 200 mg ketoconazole given 12 hourly to nine normal female subjects. No effect was noted following a single 200 mg oral dose of ketoconazole. This suppressive effect was reversible within at least 5 days of discontinuation of ketoconazole.

Adrenal Cortex↗
PubMed1983

Pharmacokinetics and bioavailability of sultamicillin estimated by high performance liquid chromatography.

Sultamicillin is an orally absorbed double ester of sulbactam (penicillanic acid sulphone, a semisynthetic inhibitor of the beta-lactamases of many Gram-positive and Gram-negative species) and ampicillin. First-pass hydrolysis of this prodrug liberates equimolar proportions of sulbactam in plasma, saliva and urine is described and was used to determine the absolute bioavailability of sulbactam and ampicillin from sultamicillin in six normal male volunteers who each received a single 750 mg oral dose of sultamicillin or an iv dose of the equivalent amounts of ampicillin (441 mg) and sulbactam (294 mg). Treatments were given in random order with not less than four days intervening. The mean peak plasma concentrations and time to peak of sulbactam and ampicillin following the 750 mg oral half lives, systemic and renal clearances for sulbactam and ampicillin were similar. The bioavailability for both drugs from sultamicillin as estimated from both plasma and urine pharmacokinetics was better than 80%. We conclude that sultamicillin is an extremely efficient prodrug for ampicillin and sulbactam and that the HPLC assay method is accurate, rapid and easier to perform than the differential microbiological assay.

Adult↗
PubMed1982

Pharmacokinetics of intravenous glibenclamide investigated by a high performance liquid chromatographic assay.

A simple high performance liquid chromatographic assay for the determination of plasma glibenclamide concentrations is described. This resolved glibenclamide from normal plasma constituents. The calibration curve of the assay was linear over the range 10-500 microgram/l and the minimum level of detection was 2 microgram/l. Within-assay coefficients of variation were 11.6% (20 microgram/l); 5.3% (50 microgram/l); 6.8% (100 microgram/l); between-assay coefficients of variation were 8.4% (20 microgram/l); 4.7% (50 microgram/l) and 7.4% (100 microgram/l). The assay was used to study the pharmacokinetics of a 1 mg intravenous dose of glibenclamide in eight normal subjects. The mean half-life was found to be 1.47 +/- 0.42 h (SD) and no evidence for a non-linear beta-phase or slowly equilibrating 'deep' compartment was found although this could not be rigorously excluded. The mean systemic drug clearance was 78 +/- 29 ml X h-1 X kg-1 and the apparent volume of distribution in the beta-phase was 155 +/- 44 ml/kg. The median time of maximum response of plasma immunoreactive insulin was 25 min and the median time of maximum blood glucose response was 53 min. No correlation could be found between the pharmacokinetics of glibenclamide and these responses in fasted normal individuals.

Adult↗
PubMed1982

Pharmacokinetics of single doses of sulphinpyrazone and its major metabolites in plasma and urine.

1 High pressure liquid chromatographic assays for the estimation of sulphinpyrazone and its sulphide, sulphone and p-hydroxy metabolites in plasma and urine are described. 2 Five normal volunteers received 200 mg and 400 mg sulphinpyrazone orally. Sulphinpyrazone was rapidly absorbed and eliminated with a half-life of approximately 4 h irrespective of dose. Peak plasma concentrations and area under the plasma concentration-time curves (AUC) were consistent with linear pharmacokinetic behaviour. 3 Plasma concentrations of the sulphone were low and peaked before those of the sulphide; its mean half-life was 3.1 h. The sulphide, which may be the sulphinpyrazone metabolite with activity on platelets, was eliminated with a mean half-life of 13.4 h. The AUC increases with dose of both metabolites suggested non-linearity. 4 Approximately 45-50% of the administered dose was eliminated in the urine as unchanged drug or as sulphone or p-hydroxy-sulphinpyrazone. The sulphide metabolite was not detected in the urine. The renal clearance of sulphinpyrazone was approximately 18 ml min-1 and that for the sulphone was similar. Sigma minus plots of the urinary excretion yielded half-lives of 3.5 h for the sulphone and 1 h for p-hydroxy-sulphinpyrazone.

Adult↗
PubMed1982

Effect of pirprofen on glibenclamide kinetics and response.

Pirprofen (a new non-steroidal anti-inflammatory agent), 200 mg 8 hourly, or placebo was administered orally to eight normal volunteers to investigate its effect on the pharmacokinetics and glucose and insulin responses after 1 mg i.v. glibenclamide. No significant changes were produced in these measures and in vitro studies showed no displacement of glibenclamide by pirprofen from plasma protein binding.

Adult↗
PubMed1981

Plasma mexiletine concentrations following combined oral and intramuscular administration.

Mexiletine in doses of 50, 100 and 400 mg was administered by intramuscular injection to a healthy subject and the resulting plasma concentrations were compared with those after 100 mg given intravenously. The bioavailability of mexiletine given by this route is complete and the kinetics are linear with dose. Plasma mexiletine concentrations resulting from 200 mg given orally with either two 4-ml intramuscular injections each containing 100 mg (Mexitil--for intravenous use) or one 2-ml intramuscular injection of an experimental preparation containing 200 mg were compared in 3 and 6 normal subjects respectively. Plasma levels within the therapeutic range of 0.75-2 microgram/ml were attained at mean times of 28.7 and 42.5 min respectively. Apart from raised plasma creatine phosphokinase levels (as would be expected following an intramuscular injection) the tolerability of intramuscular mexiletine injections was satisfactory. Further studies in patients will be required to determine whether the combined oral and intramuscular administration of mexiletine is of value in acute myocardial infarction.

Administration, Oral↗
PubMed1981

Plasma and salivary pharmacokinetics of caffeine in man.

Plasma and salivary caffeine concentrations were measured by gas-liquid chromatography in 6 healthy caffeine-free volunteers following oral administration of 50, 300, 500 and 750 mg caffeine. Caffeine was also given to a single subject intravenously in doses of 300, 500 and 750 mg. Caffeine was rapidly absorbed and was completely available at all doses. The apparent first-order elimination rate constant decreased linearly with dose and was 0.163 +/- 0.081 h-1 for 50 mg and 0.098 +/- 0.027 h-1 for 750 mg. The total body clearance was unaffected by dose and was 0.98 +/- 0.38 ml/min/kg. There was a trend towards increasing apparent volume of distribution with increasing dose. A linear relationship existed between the area under the plasma concentration, time curve and dose and dose-normalised plasma concentration, time plots were superimposable. These findings suggest that caffeine obeys linear pharmacokinetics over the dose range investigated. Despite significant inter-individual differences in pharmacokinetic parameters there was good reproducibility within 5 subjects given 300 mg caffeine orally on 3 occasions. Salivary caffeine levels probably reflect the unbound plasma caffeine concentration and can be used to estimate the pharmacokinetic parameters of the drug. Overall the saliva/plasma concentration ratio was 0.74 +/- 0.08 but within subjects some time-dependence of the ratio was found with higher ratios initially (even after intravenous administration) and lower ratios at longer time intervals after the dose. Urinary elimination of caffeine was low and independent of dose: 1.83% of the dose was eliminated unchanged.

Adult↗
PubMed1980

Effect of cimetidine on the absorption of orally administered tetracycline.

1 Six healthy female subjects received orally two 250 mg tetracycline tablets either with 400 mg cimetidine or placebo. In a separate experiment six healthy female volunteers received 500 mg tetracycline as a suspension on the fifth day of a 6 day regime of 400 mg cimetidine or placebo, 8 hourly and at bedtime. 500 mg tetracycline as tablets was also given with cimetidine only. 2 Following a single dose of cimetidine the mean peak tetracycline plasma concentration was significantly reduced by 1.2 microgram/ml and the area under the plasma concentration, time curve was decreased by 40%. The 72 h urinary tetracycline excretion was diminished by approximately 30%. 3 Tetracycline had no effect on the plasma concentration, time profile of cimetidine. 4 Administration of 400 mg cimetidine 8 hourly and at night for 6 days and dosing with 500 mg tetracycline as tablets or suspension on the fifth day produced no alteration in tetracycline kinetics. 5 It was concluded that under clinical circumstances it is unlikely that cimetidine produces a clinically significant alteration in tetracycline absorption or disposition. 6 The bioavailability of tetracycline from tablets and suspension was found to be similar (31.2% and 36.9% of the dose excreted in the urine over 72 h). 7 The mean renal clearance of tetracycline was 83.8 ml/min (95% confidence interval +/- 9.2 ml/min) and was unaltered by cimetidine treatment.

Adult↗