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D Jorkasky

Publications and source records attributed to D Jorkasky.

16 recordsLinked to original sources
PubMed2000

Steady-state pharmacokinetics of carvedilol and its enantiomers in patients with congestive heart failure.

Carvedilol is a relatively new drug with beta- and alpha 1-receptor blocking activity and antioxidant effects recently approved for the treatment of congestive heart failure (CHF). An ascending, multiple-dose study was completed in 20 male patients with stable New York Heart Association (NYHA) Class III or IV CHF. The pharmacokinetics of carvedilol, S(-)-carvedilol, R(+)-carvedilol, and the active metabolites of carvedilol was assessed at steady state after twice-daily oral administration of carvedilol for 7 days at 6.25, 12.5, 25, and 50 mg doses. Carvedilol exhibited stereoselective pharmacokinetics in CHF patients with dose-proportional increases in steady-state plasma concentrations of carvedilol and its enantiomers. Mean AUC and Cmax values for carvedilol were up to twofold higher in patients with Class IV CHF as compared to those with Class III CHF. Steady-state plasma concentrations of the active metabolites also increased in a dose-proportional manner and were typically 10% or less of that observed for carvedilol. In general, carvedilol was adequately tolerated by adult male CHF patients at the dose levels (6.25-50 mg) evaluated in this study as adverse events were consistent with those frequently observed in patients with CHF.

Adult↗
PubMed1998

Pharmacokinetics of intravenously and orally administered eprosartan in healthy males: absolute bioavailability and effect of food.

Eighteen healthy males received a single 300 mg oral dose of eprosartan as the commercial wet granulation formulation under fasting conditions and following a high-fat breakfast and a single 20 mg intravenous (i.v.) dose. The pharmacokinetics of i.v. eprosartan (mean +/- S.D.) were characterized by a low systemic plasma clearance (131.8 +/- 36.2 mL min(-1)) and a small steady-state volume of distribution (12.6 +/- 2.6 L). Oral bioavailability averaged 13.1%, due to incomplete absorption. In vitro dynamic flow cell dissolution data showed that pH-dependent aqueous solubility of eprosartan is one factor which limits absorption. Eprosartan terminal half-life was shorter after i.v. (approximately 2 h) versus oral (approximately 5-7 h) administration, which may be due to detection of an additional elimination phase or absorption rate-limited elimination following oral administration. Oral administration of eprosartan following a high-fat meal compared with fasting conditions resulted in a similar extent of absorption (based on AUC), but a decreased absorption rate. Cmax was approximately 25% lower, and a median delay of 1.25 h in time to Cmax was observed when eprosartan was administered with food. These minor changes in exposure are unlikely to be of clinical consequence; therefore, eprosartan may be administered without regard to meal times.

Acrylates↗
PubMed1997

Effect of intravenous fenoldopam on intraocular pressure in ocular hypertension.

Intravenous fenoldopam, a selective dopamine-1 receptor agonist, was compared with placebo in this randomized, double-blind, two-period crossover study to evaluate its effects on intraocular pressure, aqueous dynamics, and macular blood flow in patients with elevated intraocular pressure or primary open-angle glaucoma. Doses of fenoldopam were titrated up to a maximum of 0.5 microgram/kg/min. Intraocular pressure, measured by pneumotonometry, was the primary outcome variable. Other outcomes included macular blood flow assessed by blue field examination, visual field examined by automated perimetry, aqueous outflow facility measured by tonography, and aqueous humor production determined by fluorophotometry. During infusions of fenoldopam, intraocular pressure increased from a mean baseline level of 29.2 mmHg to a mean maximum level of 35.7 mmHg. During the placebo infusions, pressure increased from a mean baseline of 28.4 mmHg to a mean of 29.0 mmHg at the time point that corresponded to the mean maximum intraocular pressure on the day intravenous fenoldopam was administered, to yield a mean difference in pressure between study days of 6.7 mmHg (P < 0.05). There were no apparent changes in macular blood flow, visual fields, or production or outflow of aqueous humor associated with fenoldopam infusion. The increase in intraocular pressure seen in this population of patients with ocular hypertension during infusions of fenoldopam is consistent with fenoldopam-associated increases in intraocular pressure reported in previous studies of healthy volunteers and of patients with accelerated systemic hypertension. These results further suggest that dopamine-1 receptors play a role in the regulation of intraocular pressure.

Adult↗
PubMed1987

Increase in natural killer activity in cyclosporine-treated renal allograft recipients during rejection.

Natural killer (NK) activity was assessed in a prospective fashion in 15 renal transplant recipients receiving single HLA-haplotype matched allografts and maintained on cyclosporine (CYA) immunosuppression. There was marked variability in NK activity pretransplantation in this population; however, a strong correlation (r = 0.92, p less than 0.01) was found between determinations in an individual patient upon repeated testing. No significant depression of NK activity occurred within the first 12 weeks following transplantation. Whole blood CYA levels did not correlate with NK activity. Although NK activity prior to transplantation did not predict clinical outcome of the allograft, a marked rise in NK activity was observed in patients undergoing rejection compared with those not rejecting (p less than 0.01). A large increment in activity was seen in eight of 11 rejection episodes; a similar increase was rarely seen in the absence of rejection. These results indicate that NK activity is stimulated during allograft rejection in CYA treated renal transplant recipients. It remains to be determined whether this rise in NK function represents a manifestation of alloreactivity accompanying the rejection process or whether NK cells directly contribute to allograft destruction.

Adolescent↗
PubMed1986

Azathioprine and hepatic venocclusive disease in renal transplant patients.

We report 3 cases of hepatic venocclusive disease occurring in renal transplant patients receiving azathioprine and combine our experience with 4 other previously reported cases. The data suggest a clinical syndrome characterized by (a) delayed clinical onset, (b) striking male predominance, (c) presentation with jaundice followed by evidence of portal hypertension, and (d) poor prognosis. One of our patients, who is still alive 40 mo after the first onset of symptoms of liver disease, showed striking clinical improvement with discontinuation of azathioprine and subsequent deterioration on reinstitution. We suggest that azathioprine may be closely linked with the development of venocclusive disease in renal transplant patients and that the frequency of this disorder may be more common than previously reported. To attempt to prevent a fatal outcome, this group of patients should be closely monitored for the earliest signs of hepatic venocclusive disease through periodic serum bilirubin and alkaline phosphatase determinations. Patients with abnormal tests should undergo liver biopsy. If hepatic venocclusive disease is found, prompt withdrawal of azathioprine is indicated.

Adult↗
PubMed1985

Differential effects of corticosteroids on Na+ transport in rat distal colon in vitro.

We studied rat distal colon during in vitro incubation with aldosterone and dexamethasone. Both hormones caused short-circuit current (Isc) to increase with a latency period of approximately 3 h. At the 7th h of incubation, control colons had a Isc of 72 +/- 8 microA . cm-2 while tissues incubated with 10(-5) M aldosterone and 10(-8) M dexamethasone, the respective maximal stimulatory concentrations, had similarly increased Isc, 211 +/- 21 and 185 +/- 18 microA . cm-2, respectively. The increase in Isc induced by steroids reflected increased net sodium transport: control, 3.4 +/- 0.8; aldosterone, 6.7 +/- 0.7 (P less than 0.05); and dexamethasone, 7.5 +/- 1.0 mueq . h-1 . cm-2 (P less than 0.025). Spironolactone inhibited the response to both steroids, but the molar ratio of antagonist to agonist was less for aldosterone (approximately 5,000:1) than for dexamethasone (approximately 50,000:1). Amiloride inhibited a greater fraction of aldosterone-induced Isc (0.70 +/- 0.07) than that of dexamethasone (0.37 +/- 0.07; P less than 0.025). The latter value was similar to the effect of amiloride on control tissues (0.35 +/- 0.04). These data provide evidence that the cellular mechanisms by which aldosterone and dexamethasone induce Na+ transport are different.

Aldosterone↗
PubMed1985

Bartter's syndrome: a unifying hypothesis.

The most proximate defect responsible for the pathogenesis of Bartter's syndrome remains uncertain. Although an abnormality in chloride reabsorption in the thick ascending limb of Henle has been postulated, renal clearance studies performed during oral water loading failed to disclose a reduction in fractional chloride reabsorption. We alternatively postulate that the underlying abnormality may reside in a generalized increase in cell sodium permeability. Elevated levels of cell sodium may secondarily stimulate Na-K-ATPase activity. In the cells of the distal nephron, stimulated Na-K-ATPase would lead to enhanced potassium secretion into the tubular fluid producing the characteristic potassium depletion. In addition, increased cell sodium influx may stimulate a sodium-calcium exchanger. If this process exists in vascular smooth muscle, it may result in reduction of cytosolic calcium activity. This effect and/or chronic potassium depletion may mediate the reduced vascular reactivity characteristic of this syndrome.

Adult↗
PubMedDate not supplied

Acute renal allograft rejection: difficulty in diagnosis of histologically mild cases by MR imaging.

To determine the ability of magnetic resonance (MR) imaging to diagnose various degrees of acute allograft rejection (AR), 33 MR examinations in 28 patients were obtained. Surface coils were used in 21 examinations. Seventeen examinations were correlated with biopsy results, which were graded as absent (n = 7), mild (n = 6), or severe (n = 4) AR. Corticomedullary differentiation (CMD) on T1 weighted images was graded as absent/poor versus distinct, and images were also evaluated for visibility of intrarenal vessels. For serial examinations, renal volume was measured and compared. The MR results were correlated with radionuclide interpretations in 22 cases. Diminished CMD was most common with AR (7 of 12) but was also seen with acute tubular necrosis (2 of 6) and cyclosporin toxicity (2 of 3). All four cases of severe AR had diminished CMD. In contrast, only one of six cases of mild AR had diminished CMD (p less than 0.05). Four of five cases of mild AR by radionuclide scan were correctly diagnosed. Visualization of intrarenal vessels was best with surface coils, but this did not contribute to differential diagnosis. Renal volume was increased in rejecting allografts. Magnetic resonance is a promising modality for investigation of renal allografts but is not a sensitive or specific modality for the diagnosis of mild AR.

Graft Rejection↗
PubMedDate not supplied

Effect of hepatic disease on the pharmacokinetics and plasma protein binding of eprosartan.

STUDY OBJECTIVE: To evaluate the pharmacokinetics and plasma protein binding of eprosartan in hepatic disease. DESIGN: Single-dose, parallel-group study. SETTING: Oklahoma Foundation for Digestive Research, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma. PATIENTS: Eight healthy subjects with normal hepatic function and eight patients with hepatic disease. INTERVENTION: All subjects received a single oral dose of eprosartan 100 mg. MEASUREMENTS AND MAIN RESULTS: Eprosartan plasma concentrations were quantified by high-performance liquid chromatography; plasma protein binding was determined by ultrafiltration. Using analysis of variance, point estimates (PE) and 90% CIs were calculated. Total and unbound maximum concentrations and degree of plasma protein binding were similar for both groups. Total area under the plasma concentration-time curve (AUC0-t) was approximately 40% higher for the group with hepatic disease (PE 1.42, 90% CI 0.94-2.14). Similarly, unbound AUC0-t was approximately 50% higher (PE 1.53, 90% CI 0.98-2.39). CONCLUSION: Eprosartan was safe and well tolerated by both groups. Based on the increase in AUC in patients with hepatic disease compared with those with normal hepatic function, the dosage of eprosartan in patients with hepatic disease should be individualized based on tolerability and response.

Acrylates↗