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Biomedical subjects

D A Boyle

Publications and source records attributed to D A Boyle.

8 recordsLinked to original sources
PubMed1991

The effect of food on pharmacokinetics and pharmacodynamics of fenoldopam in class III heart failure.

Eighteen patients with New York Heart Association class III congestive heart failure were given single 100 mg oral doses of fenoldopam with food or fasting in a random-order single-blind crossover trial. Before and after each fenoldopam dose, thermodilution cardiac output, right atrial pressure, pulmonary artery pressure, and pulmonary capillary wedge pressure (PCWP) were measured with a balloon-tipped pulmonary artery catheter, and heart rates and blood pressures were recorded with an automated sphygmomanometer. Compared with fasting, bioavailability of fenoldopam was decreased significantly when administered with food: mean peak plasma fenoldopam level decreased from 26.5 (+/- 4.1 SEM) ng/ml to 10.9 (+/- 1.7 SEM) ng/ml (p = 0.0004) and mean area under the concentration-time curve was decreased from 44.7 (+/- 5.8 SEM) ng.hr/ml to 26.8 (+/- 4.1 SEM) ng.hr/ml (p = 0.0001). Fenoldopam administration to fasting patients resulted in decreases in mean arterial pressure, systemic vascular resistance, and PCWP and significant increases in cardiac index without change in heart rate. The maximum changes in mean cardiac index, systemic vascular resistance, and PCWP were greatest 1 hour after oral administration and did not persist beyond 3 hours after administration. In fasting patients, changes in cardiac index were correlated with plasma fenoldopam levels, whereas changes in PCWP and mean arterial pressure did not correlate significantly with the observed fenoldopam level.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1989

Evaluation of a Bayesian regression program for predicting warfarin response.

The ability of a Bayesian regression program (Warfcalc) to predict warfarin response was evaluated retrospectively in 48 inpatients and prospectively in 10 inpatients. The prothrombin ratio (PR) on the last day of inpatient therapy was predicted using zero (naive) to five sequential, daily PR feedbacks. Bias and precision were measured using mean error (ME) and mean absolute error (MAE), respectively. Root mean squared error (RMSE) was used as a combined measure of bias and precision. In the retrospective group, the use of five PR feedbacks yielded the lowest ME, MAE, and RMSE (0.22, 0.30, and 0.45, respectively). The use of two and three daily PR feedbacks resulted in larger prediction errors compared with the use of naive parameters. Further evaluation of the retrospective patient data indicated that deletion of PR feedbacks associated with an activated partial thromboplastin time greater than 100 s and exclusion of metabolic inhibitors in the estimation of warfarin clearance resulted in more reliable predictions (ME = 0.07, MAE = 0.20, RMSE = 0.28). Similarly, deletion of such PR feedbacks and metabolic inhibitors from the prospective data and use of PRs for the first 5 days of therapy yielded ME, MAE, and RMSE values of 0.07, 0.21, and 0.27, respectively. The variance for prothrombin complex activity (PCA) as a function of the variance in the prothrombin time (PT) was investigated using Monte Carlo simulation assuming four different random error models for the PT measurements. These error models yielded functions that exhibit a maximum coefficient of variation at PCA values of 40-70%.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1988

Absolute bioavailability and dose proportionality of betaxolol in normal healthy subjects.

The absolute bioavailability and dose proportionality of betaxolol [(+/-)-1-(p-[2-cyclopropylmethoxy)ethyl]phenoxy]-3- (isopropylamino)-2-propanol hydrochloride], a cardioselective beta-adrenergic antagonist effective in the treatment of angina and hypertension, was studied in 12 healthy male subjects using a four-way crossover Latin Square design. Each subject received a 10-mg iv dose administered by constant-rate infusion over a period of 30 min and three oral doses (10, 20, and 40 mg). Blood and urine were collected over a 48-h period and analyzed for betaxolol using gas-liquid chromatography with electron capture detection. Maximum concentrations occurred 3-4 h after the dose. The maximum mean (+/- SD) blood concentrations normalized to the 10-mg oral dose were 21.6 +/- 3.7, 21.1 +/- 3.7, and 22.5 +/- 4.0 micrograms/L following the 10-, 20-, and 40-mg doses, respectively. A significant lag time of 10-80 min was observed after oral doses but was not related to dose size. The terminal slope (ts), absolute bioavailability (F), and renal clearance (CLr) were likewise not affected to an important degree by dose (ts: 0.043 +/- 0.006, 0.044 +/- 0.005, 0.046 +/- 0.006 h-1; F: 0.88 +/- 0.08, 0.82 +/- 0.06, 0.84 +/- 0.07; CLr: 0.68 +/- 0.22, 0.69 +/- 0.19, 0.65 +/- 0.22 mL/min kg). Unlike many beta-adrenergic antagonists, betaxolol has a long half-life (13-20 h) and high and consistent bioavailability (70-90%), and its disposition is independent of the size of the administered dose.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Effects of long-term oral carvedilol on the steady-state pharmacokinetics of oral digoxin in patients with mild to moderate hypertension.

The effect of multiple oral doses of carvedilol on steady-state plasma digoxin pharmacokinetics was evaluated in 12 patients with mild to moderate hypertension. Area under the curve (AUC), mean maximum plasma concentration (Cmax), mean time to maximum concentration (Tmax), concentration at 24 hours after the dose (C24), creatinine clearance, renal digoxin clearance, and urinary digoxin excretion were determined after patients took oral digoxin 0.25 mg once/day for 2 weeks. Carvedilol was added to the regimen, and digoxin pharmacokinetics were assessed after 2 weeks of concurrent treatment. The AUC and Cmax for digoxin increased by 14% and 32%, respectively (p < 0.05), with no change in Tmax. The 24-hour urinary digoxin excretion and 24-hour renal digoxin clearance increased by 45% and 26%, respectively (p < 0.05), with no change in creatinine clearance. Carvedilol appears to increase digoxin's oral bioavailability as well as renal elimination. The absolute change in digoxin pharmacokinetics was small and not clinically significant. The significance of the interaction in other patient populations remains to be studied.

Administration, Oral↗