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Biomedical subjects

B N Swanson

Publications and source records attributed to B N Swanson.

At least 37 records · Page 2Linked to original sources
PubMed1984

Initial evaluation of the non-sulfhydryl-containing converting enzyme inhibitor MK-521 in hypertensive humans.

MK-521 is a new orally active, nonsulfhydryl angiotensin-converting enzyme (ACE) inhibitor. Single doses of 2.5, 5.0, 10.0, and 20.0 mg were administered to nine hypertensive patients alternating with placebo. All doses of MK-521 caused profound suppression of ACE activity for more than 24 h and decreased standing diastolic blood pressure for more than 12 h without changes in pulse rate. Although there was no further reduction in blood pressure with doses above 5.0 mg, the duration of action was prolonged for more than 24 h with the higher doses. Serum MK-521 concentrations increased with dosage, and ACE was inhibited maximally at concentrations above 10 ng/ml. In this initial study, MK-521 was well tolerated and proved to be a potent and long-acting antihypertensive agent.

Adult↗
PubMed1983

Urinary excretion of prostacyclin and thromboxane A2 metabolites after angiotensin converting enzyme inhibition in hypertensive patients.

The contribution, if any, of various prostaglandins to the antihypertensive effects of angiotensin converting enzyme inhibitors (ACEI) is controversial. We studied the effect of the ACEI captopril (CAP) on the urinary excretion of 6-keto-PGF2 alpha (6-KF), the major metabolite of the vasodilatory prostaglandin, prostacyclin, and thromboxane B2 (TxB2), the stable metabolite of the vasoconstrictor TxA2, in 8 patients with essential hypertension after placebo, two weeks of CAP 25 mg t.i.d. alone, and the same dose of CAP in combination with hydrochlorothiazide (HCTZ) 50 mg/day. Mean 6-KF and TxB2 (nmol/8 hr post-dosing, respectively) did not differ significantly with any treatment; the mean ratio of 6-KF/TxB2 was also unchanged. Likewise, the excretion of these prostaglandins was also evaluated after placebo, the ACEI enalapril (ENA) (5 or 10 mg/day), and the combination of ENA and HCTZ in another group of 8 patients with essential hypertension. Mean 6-KF and TxB2 (nmol/24 hr post-dosing, respectively) showed no significant treatment-related differences; the mean ratio was again unchanged. No correlation existed between the magnitude of blood pressure responses with any treatment and either 6-KF or TxB2 excretion. Thus, the antihypertensive action of ACEI, alone or in combination with HCTZ, does not appear to involve alterations in these vasoactive prostaglandins.

6-Ketoprostaglandin F1 alpha↗
PubMed1983

Amiodarone: individualizing dosage with serum concentrations.

The purpose of the present report is to review the available pharmacokinetic information on amiodarone with an emphasis on our own experience in monitoring serum amiodarone concentrations. We have found that 400 mg should be the maximal maintenance dose; if that treatment fails, careful addition of other antiarrhythmic agents is preferable over an increase in amiodarone dosage. Serum concentrations below 2.5 mg/L will significantly improve amiodarone's benefit-to-risk ratio.

Amiodarone↗
PubMed1983

Norfloxacin disposition after sequentially increasing oral doses.

Single doses of norfloxacin (200, 400, 800, 1,200, and 1,600 mg) or placebo were administered orally at weekly intervals to 14 healthy male volunteers in a double-blind study. Norfloxacin was measured in serum and urine by high-pressure liquid chromatography with UV detection. The concentrations of this drug in serum peaked 1 to 2 h after each dose; the mean peak values for increasing doses were 0.75, 1.58, 2.41, 3.15, and 3.87 micrograms/ml. Mean area under the serum concentration-time curves for the first 12 h after each dose were 3.56, 6.26, 11.4, 16.1, and 19.7 micrograms . h/ml, respectively. The elimination half-life of norfloxacin was about 7 h and was similar for all doses. The concentrations of the drug in urine also peaked 1 to 2 h after dosage; mean peak values for increasing doses were 200, 478, 697, 992, and 1,045 micrograms/ml. Renal clearances approximated 285 ml/min. About 30% of each dose was excreted into urine as unmetabolized norfloxacin. Crystals of the drug were occasionally observed during microscopic examination of freshly voided urine collected after the 1,200- and 1,600-mg doses. Crystalluria was not encountered at lower doses.

Administration, Oral↗
PubMed1983

Plasma platelet products and exercise-induced myocardial ischemia.

Peripheral plasma concentrations of PF-4 and TxB2 were measured by RIA in 26 patients who underwent exercise stress testing. In group A (n = 15; age 50 +/- 16, mean +/- S.D.) in whom blood sampling was performed by venipuncture, seven patients had a positive stress test associated with an increase in PF-4 concentrations from 3.3 +/- 1.6 ng/ml to 6.9 +/- 3.6 (mean +/- S.D.); six of them demonstrated a greater than 50% increase in PF-4; and only one of eight with a negative stress test had such an increase. In group B (n = 11; 49 +/- 10 yr), patients also underwent postexercise thallium-201 scanning and blood samples were obtained through an intravenous catheter. These patients consistently demonstrated higher PF-4 values (before exercise 7.5 +/- 3.9 ng/ml; after exercise 11.9 +/- 7.1), regardless of the results of the exercise and thallium studies. TxB2 concentrations were unchanged in both groups. To further evaluate the effect of catheter-collected samples on PF-4, five healthy males had serial concurrent blood sampling in opposite arms via both venipuncture and catheter. Although PF-4 concentrations in venipuncture samples were constant, those collected through the catheter increased as a function of time. On the basis of the findings in group A, enhanced platelet activation appears to be associated with exercise-induced ischemia. The observations in group B and the healthy controls indicated that catheter-collection of samples artifactually increased PF-4 concentrations.

Adult↗
PubMed1983

Dimethyl sulfoxide inhibits bioactivation of sulindac.

Sulindac, a nonsteroidal anti-inflammatory agent, is converted to a bioactive sulfide metabolite via reversible reduction of its sulfoxide moiety. To test whether DMSO can inhibit conversion of sulindac to its active form, eight healthy men received, in a randomized, crossover manner, 400 mg of sulindac, orally, either alone or 60 min after an oral dose of DMSO (30 ml, 70% solution). After the drug combination, mean plasma concentrations of the sulfide metabolite were significantly lower than in controls at 1.5, 2, 3, 4, and 8 hr after sulindac administration. The mean area under the plasma sulfide concentration-time curve for 0 to 12 hr was 30% (range 7% to 56%) lower after DMSO treatment. This study suggests that DMSO can inhibit metabolism of other sulfoxides in man and may antagonize the therapeutic efficacy of sulindac.

Adult↗
PubMed1982

Comparison of the effects of captopril, diuretic and their combination in low- and normal-renin essential hypertension.

The purpose of this study was to compare the effects of captopril (CAP) and hydrochlorothiazide (HTZ), alone and in combination, on mean (+/- S.D.) blood pressure (BP), plasma renin activity (PRA), and plasma aldosterone concentration (PAC) in equal groups of six patients with low-renin and normal-renin essential hypertension. Renin classification was determined after furosemide (80 mg) stimulation; control measurements were made after each patient had been off all medications for at least 1 week. After a single 25 mg dose of CAP, BP decreased, PRA increased, and PAC decreased more (p less than 0.05) in the normal- than in the low-renin group. Each patient was then given the following in sequence for at least 2 weeks: CAP 25 mg t.i.d., HTZ 50 mg/day, and the combination. The results at the end of each treatment period indicated a modest, but significant reduction in blood pressure in both groups following CAP and HTZ; the effect of the combination was additive. Within each renin group under similar conditions there was no significant difference in mean PRA or PAC after each treatment. Thus, while the short-term effect of CAP on BP differed in patients with low- and normal-renin essential hypertension, the effect after chronic CAP was similar, comparable to that of HTZ and additive in combination in both groups.

Adult↗
PubMed1982

Low-dose captopril: its use in mild to moderate hypertension unresponsive to diuretic treatment.

The effect of low doses (25 mg three times a day) of captopril was evaluated in 16 patients with mild to moderate essential hypertension, previously uncontrolled by hydrochlorothiazide. After a no-treatment period, mean eight-hour seated diastolic blood pressure (SDBP, mm Hg) was 103 +/- 5 on placebo, 95 +/- 8 after a single dose of captopril, 96 +/- 4 after two weeks of captopril alone, and 90 +/- 6 after its combination with hydrochlorothiazide. Though nine patients had at least a 10% fall in SDBP after the initial dose of captopril, only three had a comparable fall after two weeks; after captopril and hydrochlorothiazide, however, 12 patients had such a response. Captopril decreased mean angiotensin-converting enzyme activity and plasma aldosterone, though to a lesser extent with continued therapy. Because its side effects appear dose related, low doses of captopril combined with a diuretic are effective and may be better tolerated.

Adult↗
PubMed1982

A comparative pilot study of enalapril, a new converting enzyme inhibitor, and hydrochlorothiazide in essential hypertension.

Eight patients with essential hypertension completed a double-blind, randomly allocated crossover comparison of either 5 or 10 mg enalapril maleate, 50 mg hydrochlorothiazide, or their combination administered once daily during sequential two-week periods. Blood pressure, pulse rate, plasma renin activity, angiotensin-converting enzyme activity, plasma aldosterone concentration, and urinary electrolytes were monitored for 24 hours after placebo and on days 1 and 14 of each treatment period. After two weeks of each treatment, only the combination of enalapril and hydrochlorothiazide significantly lowered the mean seated diastolic blood pressure (SDBP). Likewise, SDBP control (less than or equal to 90 mm Hg) was achieved only after combination therapy; six of the eight patients were controlled by the combination for up to 24 hours. The initial SDBP response to combination therapy differed with the sequence of drug addition; however, by day 14 the responses were comparable, regardless of whether hydrochlorothiazide or enalapril was first given. Mean converting enzyme activity was suppressed by enalapril in all patients, though it did not always correlate with changes in SDBP or plasma aldosterone. Mean plasma renin activity increased, but the increase was significant only on the combination. There were no serious adverse effects.

Adult↗
PubMed1982

Effects of enalapril, a new converting enzyme inhibitor, in hypertension.

The new angiotensin converting enzyme inhibitor enalapril maleate was given in single oral doses of 2.5, 5, and 10 mg to 11 hospitalized patients with uncomplicated essential hypertension who were on a 150-mEq sodium diet. All doses of enalapril induced reduction of mean seated diastolic blood pressure (SDBP). The magnitude of the initial SDBP reduction was not dose related, but the duration of effect was longer (greater than 12 hr) after the 5 and 10 mg. After dosing, mean plasma angiotensin converting enzyme activity (ACE) and aldosterone concentration (PAC) fell, while plasma renin activity (PRA) rose. Serum concentrations of the active diacid from of enalapril increased linearly with dosage; ACE was inhibited maximally at concentrations above 10 ng/ml. During repeated dosing in the outpatient trial there was attenuation of the antihypertensive effect (12 to 24 hr after dosing) in eight of 10 patients. Despite dose increases only two patients achieved SDBP control (less than or equal to 90 mm Hg). In the five patients in whom 50 mg/day hydrochlorothiazide was added near the end of the trail mean SDBP was further reduced. Enalapril was well tolerated. Further studies of the drug, especially in combination with diuretic, are needed.

Adult↗
PubMed1982

Sulindac disposition when given once and twice daily.

To investigate whether sulindac once daily in the evening might be equivalent to the currently recommended twice-daily dose schedule in sustaining plasma concentrations of bioactive sulfide metabolite, 12 healthy subjects received, in a randomized crossover study, sulindac, 200 mg b.i.d. (at 9:00 A.M. and 9:00 P.M.) and 400 mg once daily (at 9:00 P.M.), each for 7 days. At steady state the area under the plasma concentration-time curve (AUC) over 24 hr for sulfide metabolite was greater after once-daily dosing (112 and 84 micrograms . hr . ml-1, P less than 0.05), while mean trough concentrations did not differ. The greater AUC seemed to be related to diurnal variation in metabolite cumulation. A circadian rhythm was apparent at steady state during twice-daily dosing; the mean AUC and peak plasma concentration (C(max)) were greater between 9 A.M. and 9 P.M. than between 9 P.M. and 9 A.M. (50 and 34 micrograms . hr . ml-1; 6.85 and 4.23 micrograms/ml). Although C(max) values of sulfide were higher after morning doses of sulindac, it was apparent that much of the plasma sulfide after morning doses was actually derived from the previous evening dose. This may be a consequence of circadian rhythm in gallbladder emptying. While renal clearance of sulindac was related to urinary pH, diurnal changes in urinary acidity did not cause the fluctuations in the plasma sulfide. Since once-daily sulindac in the evening is as, if not more, effective than twice-daily drug in sustaining plasma sulfide levels, further studies on the therapeutic efficacy of once-daily dosing are warranted.

Adolescent↗
PubMed1982

Cimetidine does not alter morphine disposition in man.

1 The pharmacokinetic parameters of morphine were determined in a crossover fashion following 4 days pretreatment with cimetidine, 300 mg every 6 h, or placebo. 2 Cimetidine had no apparent effect on the mean morphine plasma clearance, volume of distribution, AUC or half-life (P greater than 0.05; power greater than 0.80). 3 Cimetidine had no apparent effect on the magnitude or duration of morphine induced miosis. 4 The absence of a demonstrable effect on the pharmacokinetics of a drug with a high extraction ratio such as morphine suggests that cimetidine did not significantly reduce hepatic blood flow in ambulant normal volunteers.

Adult↗
PubMed1982

Determination of norfloxacin, a new nalidixic acid analog, in human serum and urine by high-performance liquid chromatography.

A high-performance liquid chromatographic method for the analysis of norfloxacin (MK-366) [1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)3-quinolinecarboxylic acid], a new nalidixic acid analog, in human serum and urine is described. A statistical evaluation of the assay data showed acceptable accuracy and precision for 0.1 to 10.0 micrograms of MK-366 per ml of serum and for 1.0 to 500 micrograms of MK-366 per ml of urine. MK-366 was extracted from serum and urine at pH 7.5 with methylene chloride and back-extracted with sodium hydroxide solution. Chromatography was performed on an anion-exchange column with acetonitrile-phosphate buffer as the mobile phase; UV absorbance was monitored at 273 nm. The method was used to measure MK-366 in clinical specimens.

Anti-Infective Agents↗
PubMed1981

Measurement of sulindac and its metabolites in human plasma and urine by high-performance liquid chromatography.

A sensitive high-performance liquid chromatography assay for simultaneous measurement of sulindac and its major metabolites was developed. The extraction methods provided greater than 89% recovery of sulindac and its sulfone and sulfide metabolites from both plasma and urine. Complete resolution and accurate detection of the three compounds was achieved with a reversed-phase column, UV detection at 254 nm and a methanol-acetate buffer mobile phase. Levels of sulindac and its metabolites were determined in plasma and urine from four volunteers after oral administration of 200 mg Clinoril. Glucuronide conjugates in urine were measured after alkaline hydrolysis.

Adult↗