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Biomedical subjects

R K Ferguson

Publications and source records attributed to R K Ferguson.

At least 37 records · Page 2Linked to original sources
PubMed1986

Effect of food on the bioavailability of lisinopril, a nonsulfhydryl angiotensin-converting enzyme inhibitor.

A randomized, two-way, crossover study was performed on 18 normal volunteers to assess the influence of food on the bioavailability of lisinopril, (1-[N2-[(S)-1-carboxy-3-phenylpropyl]-L-lysyl]-L-proline), a long-acting nonsulfhydryl angiotensin converting enzyme inhibitor. A single, 20-mg oral dose of lisinopril was administered to volunteers in the fasting state or following a standardized breakfast. Treatment periods were separated by 2-week intervals. No significant differences existed between fasting and fed regimens in the mean +/- SD area under the serum concentration-time curve (AUC0-120h; 1231 +/- 620 versus 1029 +/- 254 ng X h X ml-1), peak lisinopril serum concentration (86 +/- 48 versus 69 +/- 19 ng/mL), or time to peak lisinopril serum concentration (6.2 +/- 1.1 versus 6.8 +/- 1.0 h). Five-day urinary excretion of lisinopril was not altered by food (5.3 +/- 3.0 versus 5.1 +/- 2.0 mg). Based on the urinary data, the mean +/- SD bioavailability of lisinopril was not different following fasting or fed regimens (27 +/- 15 versus 26 +/- 10%). Unlike with captopril, food did not affect the bioavailability of lisinopril.

Adult↗
PubMed1986

Double-blind comparison of captopril and enalapril in mild to moderate hypertension.

To compare the antihypertensive and humoral effects of the angiotensin-converting enzyme inhibitors captopril and enalapril, 20 patients with essential hypertension, not receiving treatment for 2 weeks and consuming a prescribed sodium ion intake, were randomly assigned to two parallel, double-blind treatment groups with stratification based on race and untreated seated diastolic blood pressure. These groups received a placebo (day -1) followed by either captopril, 200 mg every 12 hours (n = 9), or enalapril maleate, 20 mg every 12 hours (n = 11), alone (days 1 to 14) and then with hydrochlorothiazide, 25 mg every 12 hours (days 16 to 28). Captopril and enalapril were coadministered alone (day 15) and with hydrochlorothiazide (day 29) to assess whether further decreases in blood pressure would occur. Captopril and enalapril alone caused comparable decreases (p less than 0.05) in the mean 12 hour time-averaged seated diastolic blood pressure from values on day -1 (placebo), on day 1 (11 and 9 mm Hg, respectively) and day 14 (8 and 7 mm Hg, respectively). The addition of hydrochlorothiazide further decreased (p less than 0.05) blood pressure in each group (7 and 8 mm Hg, respectively) from values on day 14. Combined use of captopril and enalapril did not result in further reduction. Coupled with the comparable changes observed in each treatment group in serum angiotensin-converting enzyme activity, plasma renin activity and plasma aldosterone concentration, these data support the view that captopril and enalapril have similar antihypertensive effects and mechanisms.

Adult↗
PubMed1986

Lethal accumulation of procainamide metabolite in severe renal insufficiency.

Four patients, 64-80 years of age, with severe renal dysfunction and heart disease received conventional doses of procainamide as treatment for cardiac arrhythmias. Serum procainamide concentrations at these times ranged from 6.2 to 13.3 micrograms/ml and were within the recently expanded therapeutic range for resistant ventricular arrhythmias. All 4 patients demonstrated marked and delayed accumulation of the active metabolite N-acetylprocainamide, with highest observed serum concentrations ranging from 42.0 to 59.4 micrograms/ml. Cardiotoxicity associated with these levels included progressive widening of the QRS and corrected Q-T intervals, induction of polymorphic non-sustained ventricular tachycardia (torsades de pointes), and severe depression of left ventricular function which appeared to be important factors in the deaths of these patients. The use of lower procainamide doses and careful anticipatory monitoring of serum concentrations of procainamide and N-acetylprocainamide are essential in this high-risk group.

Acecainide↗
PubMed1985

In vivo and in vitro inhibition of human histidine decarboxylase by (S)-alpha-fluoromethylhistidine.

Histidine decarboxylase (HDC) activity in Ficoll-Hypaque purified human peripheral blood leukocytes (PBL) was determined by measuring the formation of [3H]histamine from L-[3H]histidine. HDC activity was inhibited in vitro to more than 90% by (S)-alpha-fluoromethylhistidine (alpha-FMH) at concentrations of 10(-5) M and above. Both polymorphonuclear and mononuclear cells possessed HDC activity, but on a per cell basis the former had several-fold higher enzyme activity than the latter. In safety and tolerability studies, alpha-FMH was administered orally to healthy human subjects twice daily for 7 days at doses of 2.5, 10, 50 and 100 mg per person. A dose-dependent inhibition of HDC activity was observed in PBL that were isolated both at 12 hr after administration of the first dose of alpha-FMH and after treatment for 1 week. At the 50 and 100 mg doses of alpha-FMH, there was complete inhibition of HDC activity and partial inhibition at the 10 mg dose. Twenty-four hours after the last dose, HDC activity had recovered to 64-100%, 44-46%, and 30-52% of control values in subjects that received 10, 50 and 100 mg alpha-FMH respectively.

Carboxy-Lyases↗
PubMed1985

Effect of captopril and hydrochlorothiazide on the response to pressor agents in hypertensives.

The effect on arterial pressure of incremental doses of norepinephrine (2 to 10 micrograms/min) and angiotensin II (50 to 800 ng/min) administered over 10 min periods was studied in sodium-replete hypertensive patients after crossover oral treatments with placebo, captopril 50 mg in a single dose, captopril 50 mg three times daily for one week and hydrochlorothiazide 50 mg daily for a week. Neither captopril nor hydrochlorothiazide affected the dose response to infusions of angiotensin II. In comparison to placebo responses, however, both single and multiple-dose captopril therapy, and hydrochlorothiazide attenuated the pressor responses to infusions of norepinephrine. Captopril significantly depressed angiotensin converting enzyme activity from pre-dose levels and angiotensin II infusions significantly elevated plasma aldosterone concentrations. These results confirm findings reported for single dose captopril in normotensive volunteers and indicate that attenuation of the vascular responsiveness to sympathetic stimulation may contribute to the antihypertensive effects of captopril and hydrochlorothiazide therapy.

Adult↗
PubMed1985

Crossover comparison of captopril and propranolol as step 2 agents in hypertension.

The efficacy of captopril treatment was compared with that of propranolol in a single-blind crossover study in 14 patients with essential hypertension uncontrolled on diuretic alone. Both captopril (37.5 to 75 mg daily) and propranolol (60 to 120 mg daily), in combination with hydrochlorothiazide (50 mg daily), caused a significant fall in sitting systolic and diastolic blood pressure. Heart rate, plasma renin activity, and plasma aldosterone data were consistent with the effects of converting enzyme inhibition or beta blockade. Both drugs were well tolerated. Captopril appeared to be equivalent in efficacy and safety to propranolol when added to hydrochlorothiazide. It may be considered as an alternative step 2 antihypertensive agent, especially in patients experiencing unwanted effects on beta blockers.

Adult↗
PubMed1985

Estimation of gastric residence time of the Heidelberg capsule in humans: effect of varying food composition.

In animal and human studies, the gastric emptying of large (greater than 1 mm) indigestible solids is due to the activity of the interdigestive migrating myoelectric complex. The gastric residence time (GRT) of an orally administered, nondigestible, pH-sensitive, radiotelemetric device (Heidelberg capsule) was evaluated in three studies in healthy volunteers. In 6 subjects, the GRT of the Heidelberg capsule was compared with the half-emptying time (t1/2) of diethylenetriaminepentaacetic acid labeled with technetium 99m after a 4-ml/kg liquid fatty meal. The mean (+/-SD) GRT (4.3 +/- 1.4 h) was significantly (p less than 0.001) longer than the mean t1/2 (1.1 +/- 0.3 h); the GRT was prolonged compared with the t1/2 in each subject. In a randomized, crossover trial in 10 subjects, frequent feeding caused a dramatic prolongation in mean GRT of the capsule compared with the fasting state (greater than 14.5 vs. 0.5 h, p less than 0.005). In another crossover study in 6 subjects, the GRT of the capsule was evaluated after an overnight fast, a standard breakfast including solid food, and a liquid meal (i.e., 200 ml of diluted light cream). The mean GRT was 2.6 +/- 0.9 h after the liquid meal vs. 1.2 +/- 0.8 h after fasting (p less than 0.025). The mean GRT after the breakfast was 4.8 +/- 1.5 h, which was significantly greater than that after fasting (p less than 0.001) and after the liquid meal (p less than 0.01). These data suggest that the GRT of the Heidelberg capsule is a marker of the interdigestive migrating myoelectric complex in humans, the interdigestive migrating myoelectric complex can be markedly delayed by frequent feedings with solids, and the interdigestive migrating myoelectric complex is delayed by both liquid and solid meals.

Adult↗
PubMed1985

Sodium-losing nephropathy and nephrocalcinosis after transplantation.

Severe, prolonged sodium-wasting (up to 38% FENa) occurred in a man after he received a cadaveric-donor kidney. Posttransplantation supplementation with large amounts of saline and/or salt tablets was mandatory. Fludrocortisone had no clinically apparent effect. Plasma renin activity and plasma aldosterone concentration were markedly increased. As chronic rejection progressed, the syndrome ameliorated. Renal biopsy showed cellular rejection and nephrocalcinosis.

Adult↗
PubMed1985

Effects of cimetidine and ranitidine on the conversion of prednisone to prednisolone.

Prednisone is a glucocorticoid that must be converted in vivo to prednisolone for pharmacologic activity. We examined the effects of the H2-receptor antagonists cimetidine and ranitidine on the time course of plasma prednisolone concentrations after an oral dose of prednisone. Nine healthy men received each of three oral treatments in a double-blind, balanced, crossover manner: cimetidine (300 mg every 6 hours), ranitidine (150 mg twice a day), or placebo for 4 days, with prednisone (40 mg) taken also on day 4. Serial blood and urine samples were collected for 30 hours after prednisone dosing. Prednisone and prednisolone plasma and urine concentrations were analyzed by HPLC. No differences were found between treatments in the maximum prednisolone plasma concentration, t1/2, apparent volume of distribution, and AUC. Cimetidine reduced the mean (+/- SD) ratio of prednisone dose to the plasma prednisolone AUC (16.6 +/- 2.9 L/hr) below that ratio after ranitidine (19.2 +/- 4.2 L/hr) and placebo (19.3 +/- 2.8 L/hr), and resulted in the lowest fractional excretion of prednisolone in the urine (5.2% +/- 2.2%, 9.8% +/- 4.5%, and 12.4% +/- 4.9%, respectively). The minor alterations in prednisolone kinetics during concomitant cimetidine dosing are not likely to induce clinically significant alterations in steroid effect.

Administration, Oral↗
PubMed1985

Effect of phenobarbitone on the pharmacokinetics and tissue levels of amiodarone in the rat.

Phenobarbitone pretreatment has been shown to increase amiodarone total clearance and decrease amiodarone elimination half-life after a single intravenous amiodarone dose in the rat. Coadministration of phenobarbitone with amiodarone for 7 days resulted in decreased tissue amiodarone levels compared to controls. These results may have implications for patients undergoing therapy with amiodarone and concomitant potent enzyme inducing drugs.

Amiodarone↗
PubMed1985

Sulindac and ibuprofen inhibit furosemide-stimulated renin release but not natriuresis in men on a normal sodium diet.

We compared the effect of two commonly prescribed nonsteroidal anti-inflammatory drugs, ibuprofen and sulindac, and placebo on intravenous furosemide-induced natriuresis and renin stimulation in 11 healthy male volunteers, consuming a 100 mEq sodium, 80 mEq potassium diet. Chronic (6-day) therapy with each agent was followed by a 1-week washout period. There were no significant treatment-related differences in either urine volume or sodium excretion for any of the designated collection periods or for the cumulative value for the 4 h after furosemide administration. Similarly, differences among groups were not observed for creatinine clearance, urinary potassium and urinary chloride excretion. Mean basal plasma renin activity levels prior to furosemide administration on day 6 were significantly lower in the presence of ibuprofen (1.5 +/- 2.0 ng/ml/h;p less than 0.01) and sulindac (2,3 +/- 0.9 ng/ml/h; p less than 0.05), compared with placebo (3.3 +/- 1.1 ng/ml/h); the difference between the two NSAIDs was also significant (p less than 0.05). Mean plasma renin activity levels in the 4 h after furosemide increased significantly at all time points in comparison to basal values, but were significantly less for ibuprofen and sulindac groups in the first hour. Our data suggest that the natriuresis following intravenous furosemide in men consuming a normal sodium intake is not prostaglandin-dependent. Furthermore, the observation that sulindac suppressed basal and stimulated plasma renin activity levels, albeit to a lesser extent than ibuprofen, questions the claim that sulindac "spares' the kidney and compels further evaluation of this issue.

Adult↗
PubMed1984

Bucindolol, a beta-adrenoceptor blocker with vasodilatory action: its effect in systemic hypertension.

Bucindolol is a newly developed, nonselective beta-adrenergic blocking agent with intrinsic sympathomimetic activity and direct vasodilator properties. In 14 patients with mild to moderate essential hypertension, the effects of bucindolol, hydrochlorothiazide and their combination on blood pressure (BP), heart rate (HR) and parameters of the renin-aldosterone system were compared with those after placebo. Bucindolol's antihypertensive effect was evident within the first hour after drug administration, maximal at 2 to 3 hours, and lasted for as long as 12 hours. Compared with placebo values (108 +/- 5 mm Hg), both bucindolol (97 +/- 9 mm Hg) and hydrochlorothiazide (99 +/- 10 mm Hg) alone significantly and comparably reduced the 12-hour averaged standing diastolic BP, with the combination resulting in approximately additive effects (91 +/- 9 mm Hg). Although bucindolol alone did not affect HR, it attenuated the hydrochlorothiazide-induced increase in HR. There was a tendency for bucindolol to decrease plasma renin activity. Except for transient postural hypotension in 2 patients, bucindolol was well tolerated.

Adrenergic beta-Antagonists↗
PubMed1984

Enalapril, a new nonsulfhydryl angiotensin converting enzyme inhibitor, does not potentiate morphine analgesia.

Sprague-Dawley rats received oral doses of enalapril maleate (5 mg/kg), a potent, nonsulfhydryl, angiotensin converting enzyme inhibitor, or saline. Sixty min later, morphine sulfate, 5 mg/kg, or saline was injected subcutaneously. Response to a thermal stimulus was monitored before and up to 5 h ter morphine injection using the rat tail flick test. Serum ACE activity was greater than 90% inhibited by enalapril throughout the experiment. Enalapril did not exhibit analgesic activity nor did it potentiate morphine analgesia.

Analgesia↗
PubMed1984

Antihypertensive efficacy of once daily MK-521, a new nonsulfhydryl angiotensin-converting enzyme inhibitor.

The effects of the new nonsulfhydryl-containing oral converting-enzyme inhibitor MK-521 on blood pressure, heart rate, angiotensin-converting enzyme activity, plasma renin activity and plasma aldosterone concentration were assessed in 10 hypertensive patients. After a 2-week no-treatment period, patients received placebo and then 14 days each: MK-521 20 mg once daily, hydrochlorothiazide 50 mg once daily and the latter 2 in combination. During the last day of each treatment, the mean (+/- standard deviation) time-averaged (1- to 12-hour) standing diastolic blood pressure decreased from 106 +/- 8 (placebo) to 95 +/- 10 mm Hg with MK-521, 95 +/- 13 mm Hg with hydrochlorothiazide (p less than 0.05 vs placebo) and 88 +/- 11 mm Hg with the combination (p less than 0.05 vs all other treatments). The antihypertensive effect of MK-521 was maintained 24 hours after dosing. Heart rate did not change significantly after MK-521 treatment. MK-521 caused a marked suppression of converting enzyme activity for over 24 hours; plasma renin activity increased significantly after each active treatment and MK-521 significantly decreased the hydrochlorothiazide-induced elevation of plasma aldosterone concentration. In this short-term trial, MK-521 was well tolerated.

Adult↗