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Biomedical subjects

S H Jackson

Publications and source records attributed to S H Jackson.

At least 73 records · Page 4Linked to original sources
PubMed1988

Circadian variation in theophylline absorption during chronic dosing with a slow release theophylline preparation and the effect of clock time of dosing.

1. Eight volunteers were given seven doses of 200 mg of slow release theophylline at either 11.00 h and 23.00 h (regimen 1) or 17.00 h and 05.00 h (regimen 2). At the time of the sixth dose (60 h) hourly blood sampling was started and continued for 24 h. After at least 1 week volunteers crossed over to the other regimen. 2. Volunteers retired to bed at 23.00 h and arose after the 07.00 h sample during both regimens. 3. During regimen 1 there was a marked rise in mean tmax from 3.3 h after dosing at 11.00 h to 9.3 h after dosing at 23.00 h (P less than 0.001). There was also a fall in AUC(0,12) from 89.9 mg l-1 h after dosing at 11.00 h to 79.0 mg l-1 h after dosing at 23.00 h. There was no difference in mean Cmax values. 4. During regimen 2 these circadian changes were abolished with mean values after both dosing times lying between those observed during regimen 1. 5. A marked delay in absorption occurs at night and cannot be explained by food intake.

Circadian Rhythm↗
PubMed1988

Alpha adrenergic blocking activity of urapidil in man.

Urapidil is a new antihypertensive vasodilator agent whose pharmacologic action in man has not yet been fully defined. We have assessed the alpha adrenergic blocking activity of urapidil 15 and 30 mg given intravenously in a single blind study in 8 healthy volunteers. Urapidil produced dose-dependent parallel shift of the phenylephrine log dose/blood pressure response curve, consistent with significant competitive peripheral alpha 1 antagonism. Mean dose ratios were 2.99 and 5.48 for the 15 mg and 30 mg doses respectively. The pA2 for alpha 1 blockade is 7.3. Given these data, the major mechanism of antihypertensive effect of urapidil may be alpha 1 antagonism in the peripheral vasculature.

Adrenergic alpha-Antagonists↗
PubMed1988

A survey of analgesic drug utilization within and between clinical units in a health district.

A computer-based survey was carried out to compare analgesic prescription within and between three hospitals in a health district. More than 70% of patients in these hospitals were prescribed one or more non-steroidal analgesics, and more than 20% one or more narcotic analgesics at least on an as-required (AR) basis. The program permitted detailed monitoring of prescriptions for particular indications, and of the prevalence of potentially interacting combinations. It was also possible to compare prescribing habits with formulary recommendations. An extension of its use to other drug groups should allow monitoring of the effects of education and of introducing new drug prescribing policies locally and nationally.

Adolescent↗
PubMed1987

The analysis of dose-response curves--a practical approach.

The rationale for the objective assessment of dose-response curves (DRCs) is presented. Using data derived from isoprenaline/heart rate responses studies, two new statistical methods of objectively defining the terminal linear segment of an incomplete DRC are presented. Using data derived from phenylephrine/diastolic blood pressure response studies, the parallel shift quadratic model of Sumner et al. (1982) has been extended to include a measure of the suitability of the quadratic model for each individual data set using the Akaike information criterion. A parallel shift Emax model is proposed for complete DRCs.

Blood Pressure↗
PubMed1987

The interaction between chronic oral slow-release theophylline and single-dose intravenous erythromycin.

Eight volunteers were each given 300 mg of erythromycin lactobionate by i.v. infusion over 15 min in the presence and absence of chronic dosing with slow-release theophylline. Pharmacokinetic profiles were obtained for theophylline in the presence and absence of erythromycin and for erythromycin in the presence and absence of theophylline. A very small, clinically unimportant, but statistically significant increase occurred in mean (+/- S.E.M.) serum theophylline concentration from 4.9 +/- 0.3 mg/l to 5.2 +/- 0.3 mg/l in the presence of erythromycin (P = less than 0.01). The theophylline pharmacokinetic parameters did not change significantly. The only changes in erythromycin pharmacokinetics were an increase in the renal excretion (0-12 h) from 5.5 +/- 4.0 mg to 11.2 +/- 6.0 mg (P less than 0.03) and an increase in renal clearance (0-2 h) from 9.0 +/- 6.0 ml/min to 21.6 +/- 15 ml/min (P less than 0.05) in the presence of theophylline.

Administration, Oral↗
PubMed1986

Methods of comparing pharmacokinetics of slow release preparations: a comparison of "Theo-Dur" and "Phyllocontin" in patients with asthma.

The pharmacokinetics of two slow release theophylline preparations "Theo-Dur" (T) containing theophylline only and "Phyllocontin" (P) containing aminophylline have been compared in 12 patients with asthma. Each patient received both treatments in random order. The dose of treatment administered 12 hourly was increased or decreased to produce plasma theophylline concentrations of 10-20 mg/l at clinic visits normally 7 to 8 h after dosing. Pharmacokinetic studies were carried out after at least one week's treatment with this dose. After the first study day patients were crossed over to the second treatment at a dosage providing a similar amount of theophylline. They returned for a second study day after at least one week. Comparison of the dose corrected AUC, time to peak concentrations, within patient coefficients of variation (CV), number of concentration time points falling within 25% of Cmax and percentage fluctuations in plasma concentration showed no significant differences between the two preparations.

Adult↗
PubMed1986

The assessment of the beta-blocking activity of urapidil: a new method.

Urapidil is an antihypertensive vasodilator agent whose pharmacological action in man has not yet been fully defined. We have assessed the beta blocking activity of urapidil 15 mg and 30 mg i.v. in a single blind study of 10 healthy male volunteers. Urapidil at plasma concentrations in the same range as those shown to have antihypertensive affect did not significantly attenuate the chronotropic effect of isoproterenol. Propranolol 5 mg iv, the positive control, significantly shifted the isoproterenol dose-response curve to the right. We describe a new method of analyzing incomplete dose response curves whereby a linear terminal segment can be reproducibly defined.

Adrenergic beta-Antagonists↗
PubMed1986

A comparison of the haemodynamic effects of nifedipine, nisoldipine and nitrendipine in man.

Nifedipine (10 mg), nisoldipine (10 mg) and nitrendipine (20 mg) were given orally to 8 normal volunteers in a placebo controlled, double blind, crossover study. Blood pressure (BP), pulse (P) and systolic time intervals (STI) were recorded at time 0, 30, 60, 90, 120 min after drug administration. Adverse effects were also recorded. There was a fall in BP, pre-ejection time (PEP), PEP/LVET (left ventricular ejection time) and electro-mechanical systole index (QS2 index), and a rise in LVET index in response to the three active drugs compared with placebo. All active drugs, but not placebo, were associated with adverse effects.

Adult↗
PubMed1986

The bioavailability and pharmacokinetics of slow release nifedipine during chronic dosing in volunteers.

Eight healthy volunteers received slow release nifedipine 20 mg 12 hourly, for six doses. A nifedipine pharmacokinetic profile was performed after the fifth dosing interval using 12 sampling times over 12 h. A specific high pressure liquid chromatography (h.p.l.c.) nifedipine assay was used. Six of the volunteers subsequently received an i.v. infusion of 3.5 mg of nifedipine after an identical period (five dosing intervals) of chronic oral dosing with slow release nifedipine 20 mg 12 hourly. An identical pharmacokinetic profile was performed after the infusion. Bioavailability, clearance (CL), apparent volume of distribution (V), apparent half life (t1/2) and area under the curve (AUC) were calculated. The geometric mean apparent t1/2 for the slow release preparation was 6.3 +/- 2.0 h. In the six volunteers, the mean bioavailability was 46% (range 29-86%), the mean CL was 588.0 +/- 67.1 ml min-1, the mean apparent V was 160.1 +/- 61.7 l. The pharmacokinetics of slow release nifedipine during chronic dosing appear similar to those derived from single dose studies.

Administration, Oral↗
PubMed1986

The interaction between i.v. theophylline and chronic oral dosing with slow release nifedipine in volunteers.

Eight healthy volunteers received a 5 min i.v. infusion of lysine theophylline, equivalent to 197 mg anhydrous theophylline, both before (day 1) and during (day 5) steady state chronic oral dosing with slow release nifedipine 20 mg 12 hourly. A theophylline pharmacokinetic profile was performed on day 1 and day 5 and a nifedipine pharmacokinetic profile was performed on day 4 and day 5. The greatest difference in serum theophylline concentrations was seen at the first sampling time (5 min after completion of the infusion) with a mean concentration of 9.9 mg l-1 during nifedipine administration and 14.6 mg l-1 with theophylline alone. Thereafter, the difference fell to approximately 1 mg l-1 until 6 h when they became almost identical. Repeated measures analysis of variance using the theophylline serum concentrations at each of ten time points over 8 h as the repeated measures showed a small but significant effect of nifedipine (F(1,151) = 7.0, P less than 0.01) on serum theophylline concentrations. Mean volume of distribution (V) rose from 0.33 +/- 0.07 to 0.39 +/- 0.06 1 kg-1 corrected body weight (CBW) in the presence of nifedipine (t = 2.23, P = 0.052). Theophylline clearance, area under the curve to 8 h AUC (0-8), area under the curve to infinity AUC (0-infinity) and elimination half-life (t1/2) did not change appreciably. No statistically significant changes in nifedipine pharmacokinetics occurred in the presence of theophylline.

Administration, Oral↗
PubMed1986

Comparison of effects of lysine aspirin, soluble aspirin and conventional aspirin on buccal potential difference in healthy volunteer subjects.

The effects of aspirin, soluble aspirin and lysine aspirin on buccal mucosal potential difference (p.d.) were compared in a double-blind trial. Placebo and three doses of each preparation containing 150, 300 and 600 mg of aspirin were allocated according to a latin square design. Six volunteer subjects were studied; each received a total of 10 treatments at least 24 h apart. All doses of each preparation considered, a significant treatment effect was seen [F (d.f. = 2,306) = 6.2, P less than 0.003]. Lysine aspirin showed the least effect of the active treatments on buccal p.d. with a change from baseline of +8.5 mV compared with +13.3 for soluble aspirin +14.4 for conventional aspirin and -5.2 mV for placebo.

Aspirin↗
PubMed1985

Personality and theophylline pharmacokinetics.

Thirteen volunteers received an iv dose of theophylline followed by blood sampling for 8 h to calculate pharmacokinetic parameters. Ten patients with asthma undergoing chronic dosing with slow release aminophylline underwent 12 h of blood sampling to calculate theophylline clearance. Both groups completed an Eysenck Personality Inventory (EPI) from which was derived scores for neuroticism (N) and extroversion (E). Using multiple regression analysis no independent effect of either N or E score on theophylline clearance or half-life could be demonstrated.

Half-Life↗
PubMed1985

The relationship between clearance of theophylline and age within the adult age range.

Twenty volunteers aged between 20 and 57 years were given 197 mg of theophylline (as lysine theophylline) by iv infusion over 5 minutes to test the hypothesis that within the adult age range theophylline clearance declines with age. Samples were assayed for theophylline using the EMIT assay and clearance was determined by standard methods. Clearance values were 0.73 ml/min/kg below age 38 years and 0.75 ml/min/kg at and above age 38 years. Multiple regression analysis using age as a continuous variable showed no relationship between age and clearance.

Adolescent↗
PubMed1985

Similarity of blood pressure in blacks, whites and Asians in England: the Birmingham Factory Study.

Factory workers aged 16-64 years were screened for ethnic differences in blood pressure. The 78% response rate was evenly spread between whites (439 men; 164 women), black West Indians (173 men; 101 women) and Asians (172 men). Mean systolic and diastolic pressures by age decade in men were similar in all three groups, but there was a modest excess of both higher and lower blood pressures in blacks and Asians. Older black women had higher blood pressures than whites, but body mass indices were 2-5 kg/m2 greater. Multiple regression analysis revealed no significant effect of ethnic group on either systolic or diastolic blood pressure variance and that the higher pressures in black women were accounted for by differences in age and body mass index. The influence of body mass index was more marked on diastolic than systolic pressure. In men, alcohol intake and a family history of hypertension had small independent positive effects on systolic pressure. The lack of black/white difference in blood pressure differs from the United States results and may be due to the similarity in social class of participants. This should be confirmed in further population samples with larger numbers of black (and Asian) subjects.

Adolescent↗
PubMed1984

Persistence of divergent views of hospital staff in detecting and managing hypertension.

A questionnaire concerning views of hospital clinical staff was completed by 408 out of 542 staff (75%), comprising 214 medical staff of all clinical specialties, 106 first year clinical medical students, and 88 third year student nurses. On average 386 of 407 (95%) thought that blood pressure should be measured routinely in all inpatients but only 294 of 404 (73%) thought that this was appropriate for outpatients. Although 251 of 390 (64%) were taught to use the muffling of sounds (phase IV) as the diastolic blood pressure, only 219 of 406 (54%) actually used this phase alone. There were appreciable differences between the grades of staff in this respect, a small majority of most grades using phase IV. Roughly half (50 out of 102) of the medical student respondents were taught to use phase IV, but only 38 of 106 (36%) were actually using this phase. While only three out of 16 general practitioners were using phase IV diastolic blood pressure alone, the figure was 66 out of 88 (75%) for student nurses. The level of diastolic blood pressure at which clinicians would begin to treat a 50 year old asymptomatic man ranged from 90 to 121 mm Hg. When these figures were corrected to phase V values, assuming a 5 mm Hg difference between phases IV and V, the range was 85 to 116 mm Hg. Despite the general agreement among physicians interested in hypertension that the disappearance of sounds (phase V) should be used to denote diastolic blood pressure there is still considerable divergence of opinion among hospital medical staff.

Attitude of Health Personnel↗
PubMed1984

The disposition of inhaled lysine theophylline in volunteers.

Six healthy volunteers received an iv infusion of 317 mg lysine theophylline (equivalent to 197 mg anhydrous theophylline) in order to calculate theophylline clearance by standard methods. They subsequently received a 20 minute inhalation of nebulised lysine theophylline. Serum and salivary theophylline concentrations were measured and all saliva was collected for the first hour. From these concentrations estimates were made of the distribution of theophylline into the blood and saliva with 40% to 94% identified in the blood. Very high salivary concentrations were reached during the inhalation phase with saliva: serum concentration ratios of between 60 and 1600.

Aerosols↗