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Biomedical subjects

M J Vandenburg

Publications and source records attributed to M J Vandenburg.

At least 19 recordsLinked to original sources
PubMed1994

Dose finding studies with imidapril--a new ACE inhibitor.

1. We describe an approach involving a smaller, shorter study, leading onto a longer, larger study in which the antihypertensive effects of ascending doses of imidapril, a new ACE inhibitor, were investigated. Both studies were planned prospectively, assuming a clinically useful fall in BP to be 8 mm Hg (s.d. = 9). The studies included patients with mild to moderate essential hypertension (baseline sitting diastolic blood pressure (SDBP) 95-115 mm Hg). After a placebo run-in of 2-3 weeks patients received either placebo or imidapril 2.5, 5, 10 or 20 mg in the 2 week study (n = 91) or imidapril 5, 10, 20 or 40 mg in the 4 week study (n = 162). 2. The overall mean baseline SDBP was 103.4 mm Hg (s.d. 0.62) in the initial study and 101.5 mm Hg (s.d. 0.41) in the 4 week study. 3. Compared with placebo, imidapril 10, 20 and 40 mg significantly reduced SDBP. There was no significant difference between these doses, suggesting that 10 mg achieved maximal ACE inhibition in most patients. The 2.5 mg dose showed no significant effect. The 5 mg dose gave an intermediate effect. In both studies the overall incidence of adverse events was similar in the imidapril and placebo groups, and was not worrying.

Adolescent↗
PubMed1993

Digoxin pharmacokinetics and perindopril in heart failure patients.

The influence of chronic perindopril treatment on digoxin pharmacokinetics was investigated in 10 patients with mild chronic heart failure under stable diuretic and digitalis treatment and normal renal function. Digoxin was administered at a dose of 0.125 mg/day (n = 2) or 0.250 mg/day (n = 8). The 24-hour steady-state digoxin profile was assessed before and after concomitant administration of perindopril for 1 month at doses of 2 mg once a day for the first 8 days and 4 mg once a day for the remaining 21 days. Chronic treatment with perindopril produced no significant effect on mean (+/- standard deviation) digoxin serum area under the curve for 24 hours (17.9 +/- 7.4 versus 16.3 +/- 4.4 ng/mL.h), peak digoxin concentration (1.3 +/- 0.54 versus 1.2 +/- 0.36 ng/mL), time to peak concentration (3 versus 4 hours), and apparent oral clearance of digoxin (237.7 +/- 109.6 versus 237.4 +/- 79.5 mL/min). Clinical and biologic tolerance of perindopril was good throughout the study. Chronic administration of perindopril did not alter steady-state digoxin kinetics in patients with mild chronic heart failure and normal renal function, indicating that no adaptation of the digoxin dose is required during co-prescription with perindopril in such patients.

Aged↗
PubMed1992

Sustained-release verapamil and nifedipine in exercise-induced angina pectoris.

In a randomised, double-blind, crossover study of oral sustained-release verapamil 360 mg o.d. ('SR-verapamil') and oral nifedipine 20 mg t.d.s. in 19 patients with chronic stable angina pectoris, significantly greater improvement from baseline was seen with SR-verapamil than with nifedipine. Mean exercise duration was 380 +/- 108 s with SR-verapamil and 343 +/- 130 s with nifedipine (P less than 0.05); mean time to onset of angina was 326 +/- 79 s with SR-verapamil and 239 +/- 79 s with nifedipine (P less than 0.01); median time to 1 mm ST depression was 252 s (range 114-579) with SR-verapamil and 182 s (range 84-582) with nifedipine (P less than 0.01); mean ST depression at maximum exercise was 1.65 +/- 0.56 mm with SR-verapamil and 2.17 +/- 0.98 mm with nifedipine (P less than 0.05). Ambulatory ECG recordings indicated a trend in favour of SR-verapamil (median ST-time integral 0.00 [range 0-24.16] mm h-1 with SR-verapamil, 1.15 [range 0-12.50] mm h-1 with nifedipine, not significant). Median glyceryl trinitrate consumption was significantly lower (P less than 0.05) with SR-verapamil (0.21; range 0-1.25 per day) than with nifedipine (0.31; range 0-1.32 per day), but there was no significant difference between angina attack frequency. Adverse events were reported by two patients with SR-verapamil and nine with nifedipine. Once-daily sustained-release verapamil 360 mg has a significantly better effect on exercise tolerance than nifedipine 20 mg t.d.s. and also appears to be better-tolerated.

Adult↗
PubMed1991

Preventing fraud.

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Drug Industry↗
PubMed1988

A study of the potential pharmacokinetic interaction of lisinopril and digoxin in normal volunteers.

1. The pharmacokinetics of single oral doses of 20 mg lisinopril and 0.25 mg digoxin, given alone and together, have been studied in 12 normal young male volunteers. 2. Peak serum conc of lisinopril occurred at 6 to 8 h and were slightly higher during combined treatment. Subsequent elimination proceeded moderately rapidly in both cases, concn declining to approx. 25% of peak values in 24 h. The AUC of lisinopril was similarly slightly higher during combined treatment. 3. After lisinopril alone, urinary elimination of unchanged lisinopril was 13% dose in 72 h, and after combined therapy was 17% dose. 4. Although there were no statistically significant differences in lisinopril pharmacokinetics during single or combined treatment, serum and urinary parameters suggest that bioavailability may be enhanced slightly during combined treatment. 5. Plasma concentrations of digoxin were slightly lower and urinary excretion slightly higher during combined treatment, the mean renal clearance being 20% higher.

Adult↗
PubMed1986

Pharmacokinetics of enalapril in normal subjects and patients with renal impairment.

The pharmacokinetics of enalaprilat were studied after administration of single and multiple doses of enalapril maleate to people with normal and impaired renal function. Renal impairment was associated with higher serum concentrations of enalaprilat, longer times to peak concentrations, slower decline of serum concentrations and with reduced urinary elimination. Urinary elimination of enalaprilat was closely related to renal function. In patients with severe renal impairment (GFR values below 30 ml min-1 1.73 m-2) significantly smaller doses of enalapril maleate will be required than in patients with normal or less severely impaired renal function.

Adult↗
PubMed1986

Enalapril in moderate to severe hypertension: a comparison with atenolol.

Patients with moderate to severe essential hypertension (mean untreated supine blood pressure 190/112 mm Hg) received once daily enalapril 20-40 mg or atenolol 50-100 mg, supplemented if required by hydrochlorothiazide 25-100 mg, in a randomized observer-blind trial. Both regimens produced a highly significant reduction in supine and standing blood pressure. There was no significant difference in the antihypertensive effects of enalapril and atenolol when they were used as monotherapy. After hydrochlorothiazide was added to patients not achieving 'target' blood pressure, the fall in systolic pressure was significantly greater in the enalapril group than in the atenolol group, despite similar dosage of hydrochlorothiazide in the two groups. At the end of 6 months' treatment, a supine diastolic blood pressure of 90 mm Hg or below was achieved in 74% of patients on enalapril plus hydrochlorothiazide and 56% of patients on atenolol plus hydrochlorothiazide. This difference was not statistically significant. A small rise in plasma urea and creatinine was observed in the enalapril group and a small rise of urea only in the atenolol group. These changes were statistically significant but of uncertain clinical importance. This study confirms that once daily enalapril and atenolol, both alone and in combination with hydrochlorothiazide, are effective drugs in the management of moderate to severe hypertension.

Adolescent↗
PubMed1985

The effect of non-steroidal anti-inflammatory therapy on plasma neuropeptide concentrations in patients with osteoarthritis.

Plasma levels of the endogenous opioid peptides beta-endorphin and [Met]enkephalin were estimated in 10 osteoarthritic patients during treatment with a sustained-release indomethacin preparation (Osmosin). Significant diurnal variation of beta-endorphin levels was evident both on and off treatment (p less than 0.05, respectively), but the therapy was nevertheless accompanied by decreased morning levels of this peptide; no such changes were recorded for [Met)enkephalin. Whilst the treatment was associated with a reduction of pain, particularly in the evening (p less than 0.02), no correlation was evident between pain and beta-endorphin levels, nor between the patients' perception of pain relief and changes in beta-endorphin levels. The results suggest either that prostaglandins may be involved in the synthesis/release of beta-endorphin, or that the alleviation of stress may in turn reduce the need for continued beta-endorphin production in these patients.

Aged↗
PubMed1984

Factors affecting the reporting of symptoms by hypertensive patients.

Patients diagnosed as hypertensive have a high complaint rate, both on and off treatment and this has been postulated to be due to either their disease process, their being labelled as hypertensive, or to their treatment. Data from 6637 hypertensive patients being entered into clinical trials in general practice have been analysed to determine the relationship between the patient's age, sex, concurrent illnesses, concurrent medication, whether they were on antihypertensive treatment and the frequency of their reporting symptoms. The analysis was conducted using a multivariate technique. The frequency of reporting symptoms was greater in females than males. Those receiving antihypertensive therapy reported more symptoms than those who were not. This was notable with those receiving a beta-adrenoceptor blocker (47% of such patients complaining). Patients receiving concurrent medication were more likely to report a symptom than those not (48 compared to 37%). This was particularly noticeable if central nervous system-acting drugs were prescribed where the prevalence of symptoms was 52%. Patients already on antihypertensive treatment were more likely to be taking other medication for other conditions (37 vs 31%) than those not receiving antihypertensive treatment. Females were more likely to be taking other tablets than males (38 compared to 30%). The only symptoms which were less prevalent in those receiving treatment were headache, dizziness and breathlessness. All other symptoms were increased or unchanged in patients on antihypertensive therapy. This study indicates that present treatment for hypertension produces a high complaint rate from patients and that, when patients so complain, the possibility of their symptoms being due to their concurrent medication should be considered.

Antihypertensive Agents↗