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Biomedical subjects

D B Jack

Publications and source records attributed to D B Jack.

At least 37 records · Page 2Linked to original sources
PubMed1995

Psychometric profiling of the elderly using the Cambridge Cognitive Examination.

OBJECTIVES: To (1) build a psychometric profile of elderly subjects attending specialists day care centers and residential homes using the Cambridge Cognitive Examination (CAMCOG); (2) identify factors that are predictive of the score obtained; and (3) determine whether scores from CAMCOG and the less time-consuming Mini-Mental State Examination (MMSE) were correlated sufficiently for the latter to replace the former for general cognitive screening. DESIGN: Nonrandom convenience sampling of elderly subjects attending specialist day care centers, residential homes, and units for the elderly mentally ill. SETTING: Belfast, Northern Ireland. MAIN OUTCOME: CAMCOG and MMSE scores with age, sex, educational level, marital status, visual and hearing ability, various central nervous system diseases, and handedness as independent variables. RESULTS: Age, sex, the wearing of glasses, Parkinson's disease, stroke, and epilepsy were found to be significant predictors of the CAMCOG score. This pattern held true for the MMSE score, except for stroke. CAMCOG and MMSE scores were correlated closely, even after deletion of overlapping scores. However, the CAMCOG score showed an increasing bias when the mean score increased. The cognitive function of the subjects attending the 3 types of establishment differed significantly, with those in the residential homes being the most heterogenous. CONCLUSIONS: The subjects profiled showed significant cognitive impairment. The MMSE score appears to give much the same information as the CAMCOG score in this general screening of our patient group. The population considered is probably representative of subjects attending similar units in the United Kingdom.

Aged↗
PubMed1988

Measurement of the distribution coefficients of several classes of drug using reversed-phase thin-layer chromatography.

Using reversed-phase thin-layer chromatography, with octan-1-ol as stationary phase and phosphate buffer (pH 7.4) as mobile phase, the behaviour of different drugs at 37 degrees C was studied. Three classes of drug were examined: beta-adrenoceptor antagonists, non-steroidal anti-inflammatory agents and dihydropyridine calcium antagonists. As well as ranking these compounds in terms of their distribution coefficients, an attempt was also made to assign a quantitative value to each. For the beta-adrenoceptor antagonists this was done by using a series of published values obtained using the shake-flask technique: for the non-steroidal anti-inflammatory agents a series of standard compounds was used. No good calibration data were available for the dihydropyridine calcium antagonists, but approximate values were assigned. The results obtained were compared with other published data and the applicability of the method discussed.

Adrenergic beta-Antagonists↗
PubMed1988

The effects of ranitidine and cimetidine on the pharmacokinetics and pharmacodynamics of metoprolol.

The impact of cimetidine, ranitidine and placebo on the pharmacokinetics of metoprolol, given either as a single dose (100 mg) or for 7 days (100 mg b.d.), has been evaluated in two separate studies. The doses used were 800 mg cimetidine daily and 300 mg ranitidine daily. The subjects were all young, healthy volunteers. In the single dose study, cimetidine produced a marked increase in the peak plasma concentration of metoprolol and in the area under the plasma concentration-time curve; ranitidine had less effect, though the area under the curve was significantly greater than placebo. In the chronic dosing study, the area under the curve for metoprolol was also significantly higher on cimetidine (1796 ng h/ml; P less than 0.001) whereas the area under the curve on ranitidine (1258 ng h/ml) was comparable to that on placebo (1183 ng h/ml). Despite these drug-induced changes in plasma metoprolol concentration, neither cimetidine nor ranitidine altered the change in exercise-induced heart rate during dosing with metoprolol.

Adult↗
PubMed1987

Twelve hour (trough) plasma nifedipine concentrations during chronic treatment with nifedipine retard.

Variation in plasma nifedipine concentrations have been reported and one study has suggested the existence of a subpopulation of poor metabolisers of this drug. We have studied the variability of 12 h plasma nifedipine concentrations in 64 hypertensive patients on long-term nifedipine Retard 20 mg twice daily. A slightly skewed unimodal distribution with a modal concentration of 15 to 30 ng/ml was obtained. No relationship between 12-h plasma levels and debrisoquine hydroxylation phenotype was found.

Adult↗
PubMed1987

Inter- and intra-subject variability of nitrendipine and the effects of food.

Plasma concentrations of nitrendipine were measured, after single (20 mg) oral doses, in young healthy volunteers. On three occasions the subjects ingested the dose having fasted overnight. Data from these three occasions were used to assess variability in nitrendipine pharmacokinetics and both inter- and intra-subject variability were high. On a fourth occasion, the subjects took the tablet after a standard meal. The effects of food on nitrendipine pharmacokinetics, based on the comparison of data from the first fasting visit and the food visit, were negligible.

Adult↗
PubMed1987

Pharmacokinetic interactions between felodipine and metoprolol.

This double-blind, cross-over study in healthy male subjects evaluated the pharmacokinetics of felodipine and metoprolol given both separately and in combination. During three, five-day study periods, felodipine 10 mg b.d., metoprolol 100 mg b.d. and a combination of the two, were given in random order. There was at least a 7-day washout period between each pharmacokinetic study day. Plasma levels of unchanged felodipine and metoprolol were measured for 24 h after the last dose, on the 5th day of each treatment period. Eight subjects, aged 19-22 years, completed the study. Both felodipine and metoprolol, given alone and in combination, were well tolerated. None of the felodipine pharmacokinetic variables (tmax, Cmax, Cmin, AUC (0-12) and t1/2) changed significantly when felodipine and metoprolol were given in combination. Cmax and AUC (0-12) for metoprolol increased significantly when metoprolol and felodipine were combined, although tmax, Cmin and t1/2 for metoprolol remained unchanged. The changes in metoprolol pharmacokinetics induced by felodipine are small and unlikely to be clinically important.

Adult↗
PubMed1987

Ranitidine and cimetidine; drug interactions with single dose and steady-state nifedipine administration.

The effect of ranitidine 300 mg once daily and cimetidine 800 mg once daily on the disposition of nifedipine was studied in two groups of 12 volunteers. Both investigations were placebo-controlled cross-over studies. The first group received ranitidine, cimetidine or placebo for 5 days with 20 mg nifedipine given on the 5th day. Each period was separated by 1 week. The second group received nifedipine 10 mg three times daily for 5 days together with the H2-receptor antagonist or placebo. Cimetidine produced a significant increase in the AUC of both single and steady state dosing of nifedipine. Peak nifedipine levels were significantly increased only in the chronic dose study compared to placebo. Ranitidine did not produce any significant changes in either study.

Adolescent↗
PubMed1987

The pharmacokinetics of oxprenolol following oral and rectal dosing--a comparison of delivery systems and routes of administration.

Plasma oxprenolol concentrations were measured in eight healthy volunteers who received equivalent oral doses of the drug in the form of an aqueous solution and a 10/170 oxprenolol Oros drug delivery system. Absorption from the lower gastrointestinal tract was assessed by measurement of plasma concentrations after rectal administration of the pre-equilibrated Oros systems. Because three of the first four volunteers suffered local irritation, however, the other four volunteers received Slow Trasicor 160 mg orally as a comparative preparation. The rate of in vivo absorption after oral administration of the Oros system closely mirrored its in vitro release rate. Drug availability from Oros was reduced, however, and was equivalent to 77% of that from the oral solution. Oxprenolol was well absorbed from the rectum while the system was present in this segment of the gut. The reduced systemic availability in three of the volunteers could be accounted for largely by drug loss when the system was expelled. Slow Trasicor produced higher peaks but lower 24 h plasma concentrations than the orally administered Oros system. As judged from the relative areas under the plasma concentration-time curve, however, the availability of the drug from the two dosage forms was comparable.

Administration, Oral↗
PubMed1987

The influence of beta-adrenoceptor blockade on the lipolytic response to exercise.

The influence of beta-adrenoceptor blockade on the free fatty acid (FFA) response during and after submaximal exercise was studied in a group of normal volunteers. The study showed that the exercise-induced rise in serum FFA concentrations seen with placebo was reduced after pretreatment with propranolol. Furthermore, the palmitic, stearic, oleic and linoleic acid responses showed progressive attenuation with increasing doses of propranolol. Different beta blockers were studied using comparable doses: metoprolol and nadolol had little effect and produced FFA profiles that were similar to placebo whereas the changes on pindolol were comparable with those on propranolol.

Adrenergic beta-Antagonists↗
PubMed1986

The intra- and inter-subject variability of nifedipine pharmacokinetics in young volunteers.

Plasma concentrations of Nifedipine were measured following single oral doses of Nifedipine Slow Release (Adalat Retard) on three separate occasions to young, healthy volunteers of both sexes. Intra- and inter-subject variability were assessed by comparing the pharmacokinetic parameters, AUC, Cmax and T50%AUC. Interindividual variability was less than that observed in other studies with the beta-blockers, metoprolol and propranolol and there was no evidence of differences between the sexes.

Adult↗
PubMed1985

Separate and combined effects of nadolol and nifedipine on the cardiac response to exercise.

In a placebo controlled exercise protocol using healthy volunteers the effects of nadolol 80 mg and 160 mg orally and of nadolol 80 mg during treatment with nifedipine 20 mg 8 hourly were compared. Resting systolic and diastolic blood pressures were reduced by both nifedipine (p less than 0.05) and nadolol (p less than 0.01) acting alone. An unexpected finding was that nifedipine alone significantly inhibited exercise tachycardia (p less than 0.01) (8 to 12 h post dose). Predictably both doses of nadolol produced significant reduction in exercise tachycardia which was still apparent at 24 h. There was a linear relationship between log10 plasma nadolol concentration and reduction in exercise heart rate. The combined inhibitory effects of nifedipine and nadolol 80 mg on exercise heart rate showed partial additivity but did not summate. There was no pharmacokinetic interaction between the 2 drugs. The inhibition of exercise tachycardia by nifedipine, not previously documented, is consistent with an effect of the drug on the sinus node, as has been reported in in-vitro studies, and may contribute to the drugs efficacy in angina.

Adult↗
PubMed1985

A multiple dose comparative study of the pharmacodynamic and pharmacokinetic behaviour of polymer-matrix and Oros dosage forms of oxprenolol in healthy volunteers.

A new osmotic drug delivery system (Oros) has been evaluated in multiple-dose studies in young healthy volunteers as a sustained-release vehicle for once-daily administration of oxprenolol. Two Oros systems were examined in two separate studies, one containing 170 mg oxprenolol succinate with an initial zero-order release rate of 10 mg/h, and the other containing 260 mg oxprenolol succinate with an initial release rate of 16 mg/h. These were compared respectively with conventional oxprenolol hydrochloride (Trasicor) 80 mg twice daily and polymer-matrix oxprenolol hydrochloride (Slow Trasicor) 160 mg once daily. Variations in mean plasma levels and beta-adrenoceptor blockade (measured by inhibition of exercise tachycardia) were considerably reduced on the 10/170 Oros once-daily compared with the Trasicor 80 mg twice-daily regimen. With both formulations there was no significant change in mean plasma concentrations or areas under the curve after 8 days' treatment, and similar pre-dose plasma concentrations were obtained. There was significant inhibition of exercise tachycardia throughout 24 h after the 10/170 Oros on the eighth day. The 16/260 Oros system gave smoother pharmacokinetic and pharmacodynamic profiles, and on repeated dosing a higher mean pre-dose plasma oxprenolol concentration than Slow Trasicor. Drug availability was similar for the two dose forms, suggesting an acceptable level of absorption of oxprenolol from most of the gastrointestinal tract. On the eighth day exercise heart rate was significantly reduced throughout 24 h with 16/260 oxprenolol Oros, but only between 1 and 15 h with Slow Trasicor.

Adult↗
PubMed1985

Reproducibility of oxprenolol plasma concentrations in young female volunteers following oral administration of an oxprenolol Oros dosage form.

Plasma oxprenolol concentrations were measured in six young healthy female volunteers after single oral dosing with a 16/260 oxprenolol Oros system on three separate occasions. Reproducibility was assessed by comparing individual plasma profiles, areas under the curve, peak concentrations and times to peak. Plasma concentration-time profiles were consistent with an extended duration of drug release from the Oros system. Individual and mean profiles on the three occasions were similar, and no significant differences in mean plasma levels, or derived pharmacokinetic parameters, were detected. The mean amount of drug in eight systems recovered from faeces corresponded to 11% of the dose. Individual amounts were related to the total transit time of the system through the body. The 16/260 Oros system functioned reproducibly within the gastrointestinal tract, and in vivo absorption mirrored in vitro drug release.

Adult↗