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R D Colucci

Publications and source records attributed to R D Colucci.

17 recordsLinked to original sources
PubMed1995

Effects of felbamate on the pharmacokinetics of the monohydroxy and dihydroxy metabolites of oxcarbazepine.

The effects of felbamate on the multiple dose pharmacokinetics of the monohydroxy and dihydroxy metabolites of oxcarbazepine were assessed in a placebo-controlled, randomized, double-blind crossover study in 18 healthy male volunteers. Oxcarbazepine, 1200 mg/day, was administered on an open basis in combination with double-blind placebo or 2400 mg/day felbamate for two 10-day treatment periods separated by a 14-day washout period. Pharmacokinetic parameters of monohydroxyoxcarbazepine and dihydroxyoxcarbazepine were determined from plasma and urine samples obtained on the tenth day of each treatment period. Felbamate had no effect on monohydroxyoxcarbazepine plasma or urine pharmacokinetics compared with placebo, but it significantly increased values for dihydroxyoxcarbazepine maximum concentration and area under the curve from 0 to 12 hours, as well as urinary excretion of free and total dihydroxyoxcarbazepine. The mechanism that may account for the observations is the induction of oxidative metabolism of monohydroxyoxcarbazepine. Despite these changes, the relative amount of dihydroxyoxcarbazepine is small in comparison to monohydroxyoxcarbazepine, and antiepileptic activity is associated with monohydroxyoxcarbazepine rather than dihydroxyoxcarbazepine. Therefore we conclude that felbamate has no clinically relevant effects on the pharmacokinetics of oxcarbazepine in humans.

Adolescent↗
PubMed1995

Effects of felbamate on the pharmacokinetics of a low-dose combination oral contraceptive.

The effects of felbamate on the pharmacokinetics of a low-dose combination oral contraceptive containing 30 micrograms ethinyl estradiol and 75 micrograms gestodene were assessed in a randomized, double-blind, placebo-controlled parallel-group study in healthy premenopausal female volunteers established in a regimen of oral contraceptive use. They received either placebo or 2400 mg/day felbamate from midcycle (day 15) to midcycle (day 14) of two consecutive oral contraceptive cycles (months 1 and 2). Pharmacokinetic assessments of ethinyl estradiol and gestodene were performed on day 14 of both cycles. To determine whether ovulation occurred, plasma progesterone and urinary luteinizing hormone levels were measured, and diaries recording vaginal bleeding were kept. Felbamate treatment resulted in a significant 42% decrease in gestodene area under the plasma concentration-time curve (0 to 24 hours) (p = 0.018) compared with baseline, whereas a minor but not clinically relevant effect was observed on the pharmacokinetic parameters of ethinyl estradiol. There were no changes in the pharmacokinetics of ethinyl estradiol or gestodene after placebo treatment. No volunteer showed hormonal evidence of ovulation; however, one volunteer reported the onset of intermenstrual bleeding during felbamate treatment. Because of the effect of felbamate on the pharmacokinetics of gestodene and the report of intermenstrual bleeding, it is possible that the contraceptive efficacy of low-dose combination oral contraceptives may be adversely affected during felbamate treatment.

Adult↗
PubMed1995

Effects of felbamate on the pharmacokinetics of phenobarbital.

The effects of felbamate on the pharmacokinetics of phenobarbital and one of its main metabolites, parahydroxyphenobarbital, were assessed in a parallel-group, placebo-controlled, double-blind study, in 24 healthy volunteers. Pharmacokinetic parameters of phenobarbital and parahydroxyphenobarbital were determined from plasma and urine samples obtained after 28 days of daily administration of 100 mg phenobarbital and after a further 9 days of phenobarbital plus 2400 mg/day felbamate or placebo. Felbamate increased phenobarbital values for area under the plasma concentration-time curve from 0 to 24 hours and maximum concentration by 22% and 24%, respectively, whereas placebo had no effect. This increase was caused by a reduction in parahydroxylation of phenobarbital and possibly through effects on other metabolic pathways. Because felbamate inhibits the S-mephenytoin hydroxylase (CYP2C19) isozyme in vitro, it appears that phenobarbital hydroxylation is mediated in part by this isozyme.

Adult↗
PubMed1992

Cholecystokinin upregulation during intestinal repair.

To determine whether cholecystokinin (CCK), a small intestinal hormone, may have autocrine or paracrine functions, gene regulation in the rat stomach and duodenum has been evaluated following cytotoxic injury. We quantified total RNA, CCK messenger RNA (mRNA), total protein, small and large forms of CCK peptides and gastrin. The stomach and the intestine respond differently. Following cytotoxic injury duodenal total RNA falls (1.5 +/- 0.1 vs 0.18 +/- 0.04 mg/g P less than or equal to 0.0001), and CCK mRNA content is depleted (260 +/- 23 vs 41 +/- 8 pg CCK mRNA/duodenum P less than or equal to 0.0001), yet there is a paradoxical increase in CCK mRNA concentration (176 +/- 20 vs 303 +/- 38 pg CCK mRNA/mg total RNA P less than or equal to 0.01). Increases occurred in both molecular species of CCK peptides evaluated: CCK8 (8 +/- 7 vs 26 +/- 2 pmole/g P less than or equal to 0.0001), large forms of CCK (42 +/- 4 vs 250 +/- 27 pmole/g P less than or equal to 0.0001). By contrast, in the stomach, only decreases were observed. These data identify sites of anatomical and biosynthetic upregulation during gastrointestinal repair. Changes are dependent upon the length of the period of recovery, differ between stomach and duodenum, and may be age related. Intestinal CCK may have para- and or autocrine roles in addition to its hormone function.

Animals↗
PubMed1992

Evaluation and comparison of the adverse effects of streptokinase and alteplase.

The frequency and severity of adverse effects resulting from the administration of streptokinase and alteplase were determined in 126 consecutive patients who received standard dosages of these agents for the treatment of acute myocardial infarction. Evaluation was based on patient assessment by nursing staff, physicians, and the investigators before, during, and after thrombolytic administration. Overall, adverse effects occurred in 15 (41.7%) of 36 patients receiving streptokinase and 12 (13.3%) of 90 receiving alteplase (p = 0.001). No major bleeding or neurologic events were documented. Minor bleeding occurred in 13.9% and 7.8% of streptokinase and alteplase recipients, respectively (p = 0.47), and hypotension in 8 (22.2%) and 5 (5.6%), respectively (p = 0.01). The frequency of hypotension associated with streptokinase was significantly higher than that with alteplase. Thrombolytic-induced hypotension was easily managed and was not associated with sequelae.

Adult↗
PubMed1991

Monitoring serum digoxin concentrations during digoxin immune Fab therapy.

Measurement of serum digoxin concentrations (SDCs) is used routinely in the diagnosis of digoxin toxicity. Following administration of the antidote, digoxin immune antigen binding fragments (Fab), SDC monitoring is hampered by assay-related problems because of the presence of Fab in the serum. Recent evidence has suggested several available methods to monitor free SDC during Fab therapy. This report describes the utility of monitoring free SDC following Fab administration. Free SDCs were obtained using an ultrafiltration and fluorescence polarization immunoassay system in three patients over periods of up to 204 hours after Fab administration. In each case, the decline in free SDC was temporally related to the resolution of digoxin toxicity; in one case, digoxin intoxication recurred and was associated with a rebound increase in free SDC. In addition to the therapeutic benefits, prospective monitoring of free SDC in two of the patients also may have resulted in cost savings secondary to reduced hospital stay or less use of Fab.

Adult↗
PubMed1990

Segmental intestinal absorption of ranitidine: investigative and therapeutic implications.

The absorption of ranitidine from different segments of the intestinal tract was studied in a subject who had an anatomically divided small intestine. The results indicate that the drug is maximally absorbed from the small bowel rather than the stomach. Subsequent animal studies have shown that absorption of ranitidine in dogs is primarily duodenal followed by jejunal and ileal. The lack of gastric absorption, with predominantly small bowel absorption, may have investigational and therapeutic implications in a variety of gastrointestinal diseases.

Animals↗
PubMed1989

Visual compatibility of enalaprilat with commonly used critical care medications during simulated Y-site injection.

Physical incompatibility studies between an intravenous angiotensin-converting enzyme inhibitor, enalaprilat, and potentially coadministrable ICU medications have been performed. Forty-one medications and four solutions were evaluated. The medications were anesthetic/narcotics, antibiotics, an anticoagulant, a bronchodilator, electrolyte solutions, fluids, H-2 receptor blocking agents, steroids and vasoactive agents. There was no turbidity, precipitation, or color change caused by the admixing of enalaprilat with any of the 45 agents studied. This study did not take bioavailability into consideration.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1989

The chemical stability of captopril capsules.

Captopril therapy is effective in the management of congestive heart failure. The development of hypotension, using low or standard doses, frequently precludes many patients from continuing therapy. The use of 1 mg "microdose" captopril capsules has been used for dose titration to avoid complications associated with hypotension. This study evaluated the chemical stability of 1 mg microdose captopril capsules, extemporaneously prepared from commercially available captopril tablets for a period of 60 days which were stored in an amber vial at standard room temperature conditions. Captopril samples were analyzed in triplicate using high pressure liquid chromatographic method on days 0, 30, and 60 following perparation. There was no degradation observed on any of the sampling days. Therefore, the formulation of 1 mg captopril capsules remain stable for a period of 60 days.

Capsules↗
PubMed1989

The compatibility of nicardipine hydrochloride injection with various ICU medications during simulated Y-site injection.

Physical incompatibility studies between an intravenous calcium channel antagonist, nicardipine hydrochloride, and potentially coadministerable ICU medications have been performed. Forty-one medications and four solutions were evaluated. The medications were anesthetic/narcotics, antibiotics, an anticoagulant, a bronchodilator, electrolyte solutions, fluids, H2 receptor blocking agents, steroids and vasoactive agents. Of the forty-five substances, three showed evidence of physical incompatibility as manifested by turbidity, precipitation, or color change. All three were antibiotics. These were ampicillin, ampicillin/sulbactam sodium, and cefoperazone. We conclude that until bioavailability studies are performed these three antibiotics should not be coadministered with nicardipine HCl.

Ampicillin↗
PubMed1988

The effect of various postphlebotomy storage conditions on drug levels.

Monitoring drug levels in patients is standard practice in presentday critical care medicine. Clinical laboratories, however, are often unable to assay drug levels immediately following phlebotomy. This may result in blood samples being kept under a variety of storage conditions for nonuniform periods of time. The current study evaluated the stability of eight frequently monitored medications and one of their metabolities, in whole blood and plasma, at 4 degrees C or 25 degrees C, for up to 72 hours. The drugs included antibiotics, a bronchodilator, antiarrhythmics, and an anticonvulsant. Significant changes in drug levels were not identified at the time points studied. Our data suggests that meticulous postphlebotomy handling of blood samples may not be essential to obtain accurate levels of the drugs studied.

Animals↗
PubMed1988

Encainide.

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Anilides↗