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Biomedical subjects

R J Fruncillo

Publications and source records attributed to R J Fruncillo.

At least 19 recordsLinked to original sources
PubMed1999

Lack of pharmacokinetic interaction between oral pantoprazole and cisapride in healthy adults.

Pantoprazole, an irreversible proton pump inhibitor, may be administered with cisapride, a prokinetic agent. As increased cisapride concentrations may result in longer electrocardiogram (ECG) QTc intervals, a crossover study was conducted in healthy subjects to evaluate the oral pharmacokinetic interaction between cisapride (20 mg) and pantoprazole (40 mg). After dosing, serial blood samples and 12-lead ECGs were collected, and cisapride plasma concentrations were quantitated. For cisapride alone, mean parameter values were the following: peak concentration (Cmax), 56 ng/mL; time to Cmax (tmax), 1.7 hours; area under the concentration-time curve (AUC), 426 ng x h/mL; and terminal half-life (t1/2), 5.8 hours. Pantoprazole coadministration did not alter cisapride AUC or other pharmacokinetic parameters except for a slight 17% decrease in Cmax' resulting in 90% confidence limits of 79% to 88%, which were marginally outside strict bioequivalence limits. In addition, cisapride did not affect ECG QTc intervals, with or without pantoprazole. Therefore, no dosage adjustment is needed when pantoprazole and cisapride are coadministered.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1997

Bromfenac disposition in patients with impaired kidney function.

OBJECTIVES: To compare the pharmacokinetics of bromfenac among normal subjects and renally compromised patients and patients with end-stage renal disease. METHODS: Bromfenac pharmacokinetics were examined after a single 50 mg oral dose in 18 subjects with normal kidney function, 12 subjects with decreased kidney function, and 10 dialysis-dependent subjects. Protein binding was assessed by equilibrium dialysis. RESULTS: Mean peak concentrations and areas under the concentration versus time curve ranged from 3.3 to 3.9 micrograms/ml and 5.1 to 6.9 micrograms.hr/ml, respectively. The mean unbound fraction in the subjects receiving dialysis (0.29%) was nearly twice that in the subjects with normal kidney function (0.17%) and in the subjects with impaired kidney function (0.16%), but no differences were detected in clearance, volume of distribution, or their free fraction-corrected counterparts. Bromfenac half-life nearly doubled in the impaired and dialysis groups but was shorter than the anticipated 8-hour dose interval. Eight subjects had a total of 11 study events; none were serious and all were self-limited. CONCLUSIONS: These findings suggest that no dosage adjustment is necessary in patients with impaired kidney function, but clinical monitoring appropriate for their individual condition is recommended.

Adult↗
PubMed1995

The pharmacokinetics of venlafaxine when given in a twice-daily regimen.

The comparative bioavailability of the novel antidepressant venlafaxine and its pharmacologically active metabolite O-desmethylvenlafaxine was assessed when venlafaxine was given orally twice daily (75 mg bid) or 3 times daily (50 mg tid). Eighteen healthy subjects participated in an open-label, randomized, two-period, crossover study lasting 12 days. Each subject was randomly assigned to take venlafaxine according to a bid or a tid regimen through day 8 and was crossed over to the other regimen on days 9 to 12. The daily dose was titrated up to 150 mg/d and was held constant on days 5 to 12. Plasma samples for quantitation of venlafaxine and O-desmethylvenlafaxine were obtained during a 24-hour steady-state interval on days 8 and 12. Analysis of variance showed no significant differences between the two venlafaxine regimens for peak concentration (Cmax), area under the curve during 24 hours (AUC0-24), trough concentration, or fluctuation ratio for venlafaxine or O-desmethylvenlafaxine in plasma. The bioequivalence ratios for Cmax and AUC0-24 of both compounds were calculated to compare the bid regimen and the tid regimen. The mean value for each of the 4 ratios was between 96 and 100%, and the 90% confidence limits around each ratio were within 90 to 110%. These results indicate that dividing a daily 150-mg venlafaxine dose into 2 or 3 doses provides equivalent total exposure and peak plasma concentrations of venlafaxine and O-desmethylvenlafaxine, its active metabolite. Therefore, based on pharmacokinetic considerations, it appears that the same daily dose of venlafaxine can be given in either two or three divided doses without compromising efficacy.

Adult↗
PubMed1993

Lovastatin does not affect oral glucose tolerance in hypercholesterolemic patients.

In 15 non-diabetic Type II hypercholesterolemic patients, the effect of 80 mg lovastatin daily on oral glucose tolerance was investigated. Using a randomized, double-blind, two-panel, parallel design, patients on a low cholesterol diet received lovastatin (n = 7) or placebo (n = 8) for 6 weeks. After 6 weeks of treatment, patients receiving lovastatin had a significant reduction in total cholesterol (30%), LDL-cholesterol (36%), and triglycerides (26%). Time courses of plasma glucose and serum insulin changes from baseline after the oral glucose tolerance test were evaluated by AUC. No statistically significant differences were observed in the AUC of changes from baseline between treatment groups or within either treatment group at prestudy, 6 weeks, and poststudy. No patient had a clinically important laboratory or clinical drug-related adverse effect during the study. This study demonstrated that short-term administration of 80 mg lovastatin daily effectively lowers cholesterol without having adverse effects on oral glucose tolerance.

Adult↗
PubMed1986

Effect of renal failure or biliary stasis on the pharmacokinetics of amiodarone in the rat.

The single dose intravenous pharmacokinetics of amiodarone (50 mg/kg) were examined in rats with 72 h of biliary stasis secondary to bile duct ligation compared with paired control animals; and in rats with uranyl nitrate induced acute renal failure compared with paired control animals. Plasma and tissue levels (liver, kidney, heart, and lung) of amiodarone (1) and its N-deethyl metabolite 2 were obtained at 4 and 24 h following drug administration. Pharmacokinetic parameters were derived from plasma samples obtained over a 24-h period. Compared with controls, biliary stasis caused a decrease in the total clearance of 1 (1.74 versus 0.35 L/h/kg) and in the volume of distribution at steady state (21.1 versus 5.0 L/kg); renal failure caused a decrease in total clearance (1.67 versus 0.9 L/h/kg) and an increase in apparent elimination half-life (13.7 versus 10.1 h). Both disease processes produced significantly higher plasma levels of 1 when compared with control animals at 4 and 24 h. However, only the cholestatic animals had consistently higher tissue levels of 1 in the face of elevated plasma levels. In normal rats, no 1 or 2 was detected in the urine after a 50 mg/kg intravenous dose of 1, and less than 0.5% of the total dose of amiodarone (1) was excreted into bile by 12 h.

Amiodarone↗
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

The effect of acute hepatic injury on the disposition of vitamin A in the rat.

The distribution of vitamin A was measured in various body fluids and tissues in rats with carbon tetrachloride induced acute liver injury compared to vehicle treated controls. All rats received 25,000u of retinol palmitate intraperitoneally 24 hr prior to study and 50,000u on the day of the study. Rats with liver injury had significant elevations of unesterified retinol in plasma and saliva, and significant elevations of retinol palmitate in plasma, urine, and kidney. Also, liver disease caused a significant decrease in the liver concentration of retinol palmitate, and a significant decrease in the bile and kidney levels of unesterified retinol. These results suggest that redistribution of vitamin A from liver to other areas occurs after acute liver injury in rats. Also, increased levels of vitamin A in urine, saliva or plasma may be a noninvasive marker for liver injury in man after vitamin A challenge.

Acute Disease↗
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

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

The effect of single doses of cimetidine on estimated hepatic blood flow.

Controversy exists as to whether H2-receptor antagonists decrease hepatic blood flow. This study examined the effect of single doses of cimetidine 300 and 600 mg po on apparent hepatic blood flow as estimated by indocyanine green (ICG) clearance. A double-blind, repeated-measure study was performed in nine supine healthy men. Following an overnight fast, placebo or cimetidine was administered one hour prior to ICG 0.5 mg/kg iv. Plasma samples were obtained serially for a period of 20 minutes following dye administration and stored at -70 degrees until high performance liquid chromatographic analysis. Cimetidine had no apparent effect on mean +/- SD ICG clearance following placebo, cimetidine 300 mg, and cimetidine 600 mg (366 +/- 66 vs. 336 +/- 55 vs. 350 +/- 58 ml/min/m2, respectively; NS). Corresponding values for estimated hepatic blood flow were 632 +/- 109, 580 +/- 103, and 617 +/- 112 ml/min, respectively; NS. No statistically significant changes in ICG half-life or volume of distribution at steady state occurred as a function of treatment. Contrary to previous reports, single-dose cimetidine administration appeared to have no appreciable effect on hepatic blood flow. These results implicate cimetidine binding to the cytochrome P-450 system as the sole mechanism responsible for inhibition of the systemic clearance of co-administered drugs metabolized by the liver.

Adult↗
PubMed1985

Effect of amiodarone on the pharmacokinetics of phenytoin, quinidine, and lidocaine in the rat.

Previous studies have shown that amiodarone can depress certain aspects of hepatic drug metabolism in the rat. This effect was assessed in vivo by investigating the single dose intravenous pharmacokinetics of phenytoin (10 mg/kg), quinidine (25 mg/kg) and lidocaine (7.5 mg/kg) in rats pretreated for three days with a single daily 100 mg/kg intraperitoneal dose of amiodarone hydrochloride. Compared to vehicle treated controls, significant reductions of 61% and 35% in the respective total clearances of phenytoin and quinidine were observed in the presence of amiodarone. Likewise, the elimination half-lives of phenytoin and quinidine were also significantly prolonged after amiodarone pretreatment. Lidocaine pharmacokinetic parameters were unchanged in the presence of amiodarone. These results suggest that altered hepatic drug clearance may play a part in the recently described clinical drug interactions between amiodarone and either phenytoin or quinidine.

Amiodarone↗
PubMed1984

Pharmacokinetics of pentobarbital, quinidine, lidocaine, and theophylline in the thermally injured rat.

Previous studies have shown that rats with 15% third-degree burns show a severe depression in various in vitro hepatic drug-metabolizing enzymes. This effect was assessed in vivo by measuring the disposition of four liver-metabolized drugs in 16% third-degree burned rats at 7 d postburn. Compared with pair-fed control rats, pentobarbital demonstrated a significantly prolonged clearance and elimination half-life without a change in volume of distribution. Quinidine demonstrated a significantly increased volume of distribution and a significantly decreased clearance without a change in elimination half-life. Lidocaine showed a significantly increased volume of distribution. Theophylline, which is only 50% metabolized in the rat, showed no changes in any pharmacokinetic parameters. The free drug fractions of quinidine and lidocaine were found to be significantly decreased at 1 d postburn and normal at 7 d postburn. These results warrant pharmacokinetic studies in human burn patients.

Animals↗
PubMed1983

Effect of cimetidine on the pharmacokinetics of quinidine and lidocaine in the rat.

Because of previously reported drug interactions involving cimetidine and liver-metabolized drugs, the intravenous pharmacokinetics of quinidine (25 mg/kg) and lidocaine (15 mg/kg) were investigated in anesthetized rats pretreated with a single intraperitoneal dose of cimetidine (60 mg/kg) and compared with saline pretreated controls. Significant reductions of 35 and 23% in the respective total clearances of quinidine and lidocaine were observed in the presence of cimetidine. The quinidine volume of distribution was significantly decreased in the cimetidine-treated rats, while the lidocaine volume of distribution was not altered significantly. There was no significant change in the elimination half-life for either drug in the presence of cimetidine. These results suggest cautious use of quinidine or lidocaine when cimetidine is prescribed concurrently.

Animals↗